Transapical intramyocardial septal microwave ablation in treatment of hypertrophic obstructive cardiomyopathy: 12-month outcomes of a swine model.

BACKGROUND: To date, the extended Morrow procedure is considered the gold standard treatment for patients with obstructive hypertrophic cardiomyopathy who experience severe symptoms and are unresponsive to medication treatment. We therefore aimed to perform transapical intramyocardial septal microwave ablation to reduce the thickness of the interventricular septum myocardium in a minimally invasive method. METHODS: Fourteen swine were divided to form either a microwave ablation group (n = 7) or a sham group (n = 7). In the microwave ablation group, a transapical microwave antenna was inserted into the septum to ablate each myocardial segment at 40 W for 1 min, while in the sham group, the same operation was performed but without power output. We used echocardiography, electrocardiogram, during the operation. And added computerized tomography, cardiac nuclear magnetic resonance during follow-up. RESULTS: Segment hypokinesis was observed in all swine immediately following ablation. Compared with the sham group, the thickness of ablated segments in the ablation group decreased significantly 1 month post-operation (ablation group, 5.53 ± 1.00 mm vs. 8.03 ± 1.15 mm, respectively, P < 0.01; sham group, 8.40 ± 0.94 mm vs. 8.21 ± 1.09 mm, respectively, P = 0.081), and the outcome was still observed 1 year post-operation (ablation group, 3.36 ± 0.85 mm vs. 8.03 ± 1.15 mm, respectively, P < 0.01). No perforation of the septum was observed during the procedure or follow-up, and no heart failure or sudden cardiac death occurred during postoperative feeding. CONCLUSIONS: Transapical intramyocardial septal microwave ablation can effectively and safely produce a large region of necrosis. This technique can potentially mimic surgical myectomy while avoiding cardiopulmonary bypass and median sternotomy in high-risk hypertrophic obstructive cardiomyopathy patients.

Renal function improvement correlates with 3D echocardiographic findings: Effect of surgical mitral valve repair.

BACKGROUND: The association between surgical treatment of mitral regurgitation (MR) and renal function is not sufficiently well-known. We tried to evaluate renal function before and after the procedure of surgical mitral valve repair (SMVR) in degenerative severe MR. METHODS: Patients with primary severe (4+) MR and normal left ventricular ejection fraction (LVEF) that underwent SMVR, examined by a cutting-edge 3-dimensional (3D) echocardiographic probe were enrolled in this study. We took three CKD-EPI equations to measure estimated glomerular filtration rate (eGFR) before SMVR and shortly before patients discharge. A total of 40 patients with baseline lower mean eGFR were evaluated. RESULTS: Measurements substantiated statistically significant improvements in eGFR (p < 0.001), multivariable linear regression modeling indicating prominent associations between increase in eGFR and decrease of MR (p = 0.003), decline of pulmonary arterial systolic pressure (p = 0.018), as well as increment of forward stroke volume (p = 0.02), in spite of LVEF reduction, left ventricular global longitudinal strain worsening and left atrial ejection fraction impairment. CONCLUSIONS: Renal function improves after SMVR in patients with degenerative significant MR and preserved LVEF, regardless of cardiac functional worsening.

Efficacy and safety of PD-1/PD-L1 inhibitors-based immunocombination therapy versus sunitinib in the treatment of advanced renal cell carcinoma: a Meta-analysis / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：系统评价基于PD-1/PD-L1抑制剂的免疫联合治疗（以下称“免疫联合治疗”）对比舒尼替尼治疗晚期肾细胞癌（RCC）的安全性和有效性。方法：检索PubMed、Embase、Cochrane Library及中国知网（CNKI）数据库，收集国内外公开发表的免疫联合治疗对比舒尼替尼应用于晚期RCC的随机对照试验（RCT），检索时间均为自建库时间至2022年10月。由两名研究者独立评价纳入研究的质量、提取资料并交叉核对，采用StataMP16.0软件进行Meta分析。结果：共纳入6项RCT，Meta分析结果显示，（1）有效性：与舒尼替尼相比，免疫联合治疗显著提高了晚期RCC患者的总生存期[OS，HR=0.74，95% CI （0.67，0.80），P<0.01]和无进展生存期[PFS，HR=0.66，95% CI （0.51，0.81），P<0.01]；（2）安全性：两治疗组均有较高的不良反应（AE）发生率，差异无统计学意义。但免疫联合治疗组发生皮肤及内分泌系统AE显著高于舒尼替尼治疗组，而血液系统相关AE则明显低于舒尼替尼治疗组；（3）以1%为临界点，免疫联合治疗组的RCC患者，无论是PD-L1阳性或阴性的，其OS和PFS均高于舒尼替尼组。结论：免疫联合治疗可显著延长晚期RCC患者的OS和PFS，但不同系统发生AE有差异，且RCC患者PD-L1表达状态（1%为临界点）并不影响免疫联合治疗的获益。

Percutaneous Ventricular Restoration Prevents Left Ventricular Remodeling Post Myocardial Infarction: One-Year Evaluation of the Heartech First-in-man Study.

BACKGROUND: This is first-in-man investigation of an implantable Heartech left ventricular partitioning device (LVPD) therapy for chronic heart failure (HF) after a myocardial infarction. METHODS AND RESULTS: Initially, 16 patients were chosen from 3 cardiac centers within China. All patients were treated with percutaneous ventricular restoration involving the Heartech LVPD implantation. Major adverse cardiovascular and cerebrovascular events were documented. Functional status, echocardiograph evaluation, European five-dimensional health scale, 6-minute walk test before the procedure and at postoperative follow-ups were recorded. We demonstrated successful implantation and device function with a success rate of 93.75%. One patient suffered a fatal myocardial infarction within the 12 ± 1 month follow-up. However, other patients did not report any major adverse cardiovascular and cerebrovascular events at their 12 ± 1 month follow-ups. After the operation, the average left ventricular end-systolic volume index decreased dramatically (66.00 mL/m2, interquartile range [IQR] 63.00-89.00 mL/m2 vs 48.00 mL/m2, IQR 32.25-68.25 mL/m2, P = .001), along with the left ventricular end-diastolic volume index (105.00 mL/m2, IQR 90.00-130.00 mL/m2 vs 76.50 mL/m2, IQR 57.75-120.25 mL/m2, P = .002). The left ventricular ejection fraction (35.00%, IQR 27.00-38.00% vs 42.50%, IQR 34.75-50.25%, P = .003), 6-minute walk test (383.13 ± 108.70 m vs 491.17 ± 118.44 m, P = .01), and European five-dimensional health scale (65.93 ± 11.25 vs 82.50 ± 5.44, P < .001), in turn, improved significantly. CONCLUSIONS: In our study, the Heartech LVPD was demonstrated as both safe and effective in reducing LV volume, enhancing LV function after implantation. These results remain constant at least till the 12 month follow-up. (Trial Registration: NCT02938637.).

Reliability and feasibility of automated function imaging for quantification in patients with left ventricular dilation: comparison with cardiac magnetic resonance.

Automated function imaging (AFI, GE Healthcare) is a novel promising algorithm of speckle-tracking echocardiography that combines two-dimensional strain and AI technology. It shortens the analysis time, saves the cost associated with streamlining of image acquisition, rapid analysis, and reporting, and has greater accuracy and reproducibility of measurements. This study aimed to evaluate the reliability and feasibility of AFI for the quantification of left ventricular (LV) volumes and function in patients with LV dilation by comparison with CMR. We retrospectively studied 50 patients with LV dilation on echocardiography whom both underwent CMR and coronary angiography within three days. LV volumes, ejection fraction (EF), and global longitudinal strain (GLS) were measured from 3 long-axis cine-views via the AFI technique in two modes: without editing (auto-AFI) and with partial border editing (semi-auto-AFI). The LV volumes and EF were also measured with 2D Simpson's biplane method, and CMR, as the standard method, was used for comparison. The AFI method still had significantly underestimated the LV volumes compared with CMR (P<0.01), but there were no significant differences between the AFI method and the conventional Simpson's biplane method. There were no significant differences in EF between CMR and the AFI method with good correlations (auto-AFI: r = 0.81, semi-auto-AFI: r = 0.86). The auto-AFI method provided the most rapid analysis and excellent reproducibility, while the semi-auto-AFI method further improved measurement accuracy. However, there were no significant differences in LV volumes and EF between these two AFI methods. The accuracy of AFI seems to be more affected by the image quality than the left ventricular morphology.  AFI enables accurate, efficient, and rapid evaluation of LV volumes and EF in patients with dilated LV, with good reproducibility and correlations with CMR.

Heartech® left ventricular partitioning device improves left ventricular systolic function of patients with chronic heart failure post-myocardial infarction at 1-year follow-up.

OBJECTIVES: This study presents 1-year follow-up data of echocardiographic outcomes in patients who received the Heartech® left ventricular (LV) partitioning device (LVPD) (Xinrui Medical Equipment Co. Ltd., Shanghai, China). BACKGROUND: Our first-in-man study of the Heartech® LVPD confirmed its safety and efficacy in patients with chronic heart failure (HF) post-myocardial infarction (MI) 1 month post-implantation. This subsequent study reports the echocardiographic outcomes of these patients at 1 year of follow-up. METHODS: Fifteen patients with HF post-MI from three cardiac intervention centers in China were successfully implanted with the Heartech® LVPD via percutaneous ventricular restoration procedures. Echocardiographic parameters-including LV systolic function, diastolic function, two-dimensional speckle-tracking analysis, and right ventricular systolic function-were obtained before device implantation and at 1 month and 1 year postoperatively. RESULTS: There was no deterioration of LV diastolic function, specific strain parameters, or right ventricular function at 1 year. Relative to the echocardiographic parameters recorded before the procedure, the LV ejection fraction (32.47 ± 6.98% vs. 42.5 ± 7.41%; p = .001) was significantly improved at 1 year, while the LV end-diastolic volume index (106.29 ± 28.01 vs. 83.30 ± 31.71; p = .005) and end-systolic volume index were significantly reduced (72.47 ± 22.77 vs. 50.00 ± 19.70; p = .001). CONCLUSIONS: One-year echocardiographic follow-up results confirmed that no deterioration of LV diastolic function or specific strain parameters was observed and LV systolic function was significantly improved in patients with HF post-MI who were implanted with the Heartech® LVPD.

Depletion of ß3-adrenergic receptor relieves pressure overload-induced cardiac hypertrophy and heart failure via enhancing innate immune response.

Cardiac pressure overload is a crucial risk factor for cardiac hypertrophy and heart failure. Our previous study showed that depletion of the ß3-adrenergic receptor (ADRB3) induced left ventricular diastolic dysfunction via potential regulation of energy metabolism and cardiac contraction. However, the effects of ADRB3 on pressure overload-induced heart failure remain unclear. In the present study, systemic ADRB3-knockout mice suffering from transverse aortic constriction (TAC) surgery were used to identify the effects of ADRB3 on pressure overload-induced heart failure. Compared to wild-type mice, ADRB3 depletion significantly improved the left ventricular ejection fraction, reduced left ventricular posterior wall thickness and interventricular septum thickness, and decreased the area of cardiomyocytes after TAC. RNA sequencing and bioinformatics analysis showed that ADRB3 depletion up-regulated 275 mRNAs and down-regulated 105 mRNAs in mice suffering TAC surgery. GO analysis, GO-tree analysis, and GSEA showed that ADRB3 depletion mainly enhanced the innate immune response of hearts in cardiac pressure overload mice. In addition, pathway analysis and Pathway-Act analysis presented that innate immune response-related pathways, including RIG-I-like receptor signaling pathway, antigen processing and presentation, Toll-like receptor signaling pathway, and cell adhesion molecules, were significantly enriched in ADRB3-KO-TAC mice. Ten hub genes were identified using protein-protein interaction network, MCODE, and cytoHubba analysis. Furthermore, the depletion and activation of ADRB3 validated the effects of ADRB3 on the innate immune response of hearts after TAC. In conclusion, ADRB3 depletion relieves pressure overload-induced cardiac hypertrophy and heart failure, and these effects could be explained by the enhancement of innate immune response.

Risk factors for right ventricular dysfunction in patients with lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by diffuse cystic lesions of the lung. The present study was designed to evaluate the right ventricular (RV) function in LAM patients via single-beat real-time three-dimensional echocardiography (RT-3DE) and to investigate the factors affecting RV function in LAM patients. According to tricuspid regurgitation velocity (TRV), forty-five female LAM patients [(44.07 ± 10.22) years old] were divided into TRV ≤ 2.8 m/s group (n = 29) and TRV > 2.8 m/s group (n = 16). Relative echocardiography parameters were assessed by conventional transthoracic echocardiography, Doppler tissue imaging (DTI) and RT-3DE, respectively. Pulmonary function tests and the six-minute walk tests (SMWT) were also performed for LAM patients. We found that most of RV functional parameters in LAM patients were worse than that in control patients, although left ventricular dysfunction was not significantly observed. Correlation analysis showed that 3D echocardiographic RV ejection fraction (RVEF) was negatively correlated with pulmonary vascular resistance (PVR), TRV, and the decrease of oxygen saturation (SpO2) post SMWT, and positively correlated with Forced expiratory volume in the first second/forced vital capacity, carbon monoxide diffusion predicted value, SMWT distance, and resting SpO2 in LAM patients. Multivariate stepwise linear regression analysis showed that PVR and SpO2 before SMWT were independent influence factors of RVEF in LAM patients. In this study, we found that RV dysfunction was presented in LAM patients, although left ventricular dysfunction was not significantly obvious. The main influence factors of RVEF were PVR and hypoxia. RT-3DE is a low-cost and noninvasive way to evaluate RV function in LAM patients.

Global study on slope instability modes based on 62 municipal solid waste landfills.

This study summarized global examples of landfill slope instability over the past 40 years, then selected 62 cases from 22 different counties to analyse the primary factors causing landfill instability. Three slope instability modes in landfill were categorized according to the position of the slip surface: (1) slip surfaces generated inside the waste pile; (2) slip surfaces that pass through the foundation soil; and (3) slip surfaces that occur along the interface between the bottom liner and the municipal solid waste (MSW) pile. These three types of slope instability modes account for 69.4%, 19.32% and 11.28% of all slope instability, respectively. Moreover, five primary causes of landfill instability were identified. A high landfill leachate level was the dominant cause, accounting for 40.32% of cases. This was followed by inadequate compaction of MSW, which accounted for 22.58% of cases, and insufficiently bearing capacity of the foundation, which accounted for 19.35% of cases. Moreover, low shear strength of the liner-MSW interface and rapid release or deflagration of landfill gas were critical factors affecting landfill stability. Factors of safety were calculated using GeoStudio software for selected landfills in China (Maoershan and Xiaping) and Sri Lanka (Meethotamulla). Results from this study are expected to contribute to the prevention and control of landfill failure.

Compression behaviors of mechanically biologically treated wastes of Tianziling landfill in Hangzhou, China.

This study aimed to investigate the compression behaviors of mechanically biologically treated (MBT) wastes. For this purpose, the short-term compression-rebound and long-term compression tests were conducted on MBT wastes collected from Hangzhou Tianziling landfill in China. The results showed that the duration of immediate compression was obtained as 15.17-36.67 h and was comparable to municipal solid waste (MSW). The immediate compression ratio was 0.233-0.247, and it was comparable to the aged high food waste content (HFWC)-MSW, fresh and aged low food waste content (LFWC)-MSW, but much lower than the fresh HFWC-MSW. The mechanical creep ratio (C'αc) was 0.012-0.018, being close to the fresh and aged MSWs. The bio-induced compression ratio (C'αb) was 0.143-0.174. The compression ratio rose exponentially with temperature (5-42 °C) in both mechanical creep stage and bio-induced compression stage, and it increased much faster in the bio-induced compression stage. The resilient strains was only 2.1-3.3% of the compression strain at the same stress interval, suggesting that the compression strain consisted of mostly plastic deformation and negligible elastic deformation. The above findings can provide a reference for settlement prediction and storage capacity estimation of an MBT waste landfill.

Evaluation of cardiac dysfunction in adult zebrafish using high frequency echocardiography.

AIMS: Recently, the zebrafish has gained attention as an innovative experimental model to decipher molecular and cellular mechanisms involved in cardiovascular development and diseases. Nevertheless, the use of zebrafish models has been challenged because the transparency of these fish, which allows for accurate cardiac evaluation, disappears in adulthood. In this study, the epicardial outline method was performed to investigate the feasibility of echocardiography in assessing cardiac function in pathological adult zebrafish. MATERIALS AND METHODS: We attempted to estimate heart failure in adult zebrafish treated with three distinct regulators of cardiac function: phenylhydrazine hydrochloride (PHZ), doxorubicin (DOX), and ethanol. B-mode and Doppler images were evaluated at frequencies of up to 50 MHz and 40 MHz, respectively. The correlation between alterations in cardiac function, haemoglobin concentration, and myocardial histopathology were assessed. KEY FINDINGS: Cardiac output (CO) in PHZ-treated zebrafish was significantly higher than that in control zebrafish (151 ± 67 vs. 84 ± 37 µl/min, P = 0.004), whereas ejection fraction (EF) was lower (36.3 ± 10.9 vs. 50.9 ± 8.7%, P < 0.001), indicating typical high output heart failure derived from anaemia. Additionally, ventricular dysfunction in DOX-treated zebrafish was characterised by low CO (57 ± 38 µl/min) and EF (28.8 ± 10.4%), accompanied by an enlarged ventricle in diastole and systole, representing low output heart failure. For ethanol-treated zebrafish, EF was markedly reduced (39.6 ± 7.2%) indicating a dilated heart, while CO remained unchanged (90 ± 40 µl/min). SIGNIFICANCE: The epicardial outline method is an effective way of using echocardiography to assess cardiac dysfunction in pathological adult zebrafish, unlocking a major bottleneck in this research field with limited cardiac functional assays.

Administration of trastuzumab with heart irradiation induced acute cardiotoxicity in mice.

Cardiac toxicity is one of the major advese effect associated with thoracic irradiation. Breast cancer patients with human epidermal factor receptor-2 (Her-2) overexpression could be indicated for both radiation and anti-Her2 target therapy. We aimed to investigate the early detection of radiation and Trastuzumab (TRZ) induced acute cardiotoxicity in mice. In the present study, the heart of animal was subjected to irradiation (IR, 14 Gy/1 Fx), TRZ was intraperitonealy (i.p.) administrated to mice in 2 weeks (6 fractions). The IR plus TRZ group received heart IR after TRZ. We found that body weight of mouse in treatment groups reduced significantly as compared with that of mouse in control group (P<0.05). At day 21, the diastolic function of mice decreased significantly in IR plus TRZ group compared with control group measured by E/E' parameter using echocardiography (57.72 vs 40.82, P<0.05). The left ventricular posterior wall (LVPW) and interventricular septum (IVS) were also increased significantly in diastolic phase at day 21 in the combined group compared with TRZ alone (LVPW: 0.95 mm vs 0.70 mm, P<0.05; IVS: 0.94 mm vs 0.65 mm P<0.05). Moreover, hematoxylin and eosin (HE) staining of cardiac tissue showed that the arrangement of myocardial cell was disordered in the combined group with vacuolar and adipocyte changes, as well as the loose of structure of myocardial cells and the pyknosis of the nucleus. Moderate damage was observed in irradiation-treated group and TRZ-treated group. The expressions of γ-H2AX, vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand Factor (vWF) were remarkedly appeared in co-treatment group. Heart irradiation combined with TRZ treatment simultaneously might cause acute cardiac toxicity in terms of the parameter of E/E', LVPW and IVS. Our results suggest that the diastolic function could detect the early stage of acute cardiotoxicity in heart exposed to irradiation and TRZ co-treatment in mice. The DNA injury and microangiopathy might involve in cardiac injury that aggravated by radiation and Trastuzumab treatments.

Laboratory study on the hydraulic characteristics of mechanically and biologically treated waste in China.

Mechanical biological treatment (MBT) can greatly reduce the amount of municipal solid waste (MSW) and has become a hot topic in environmental geotechnical engineering. To study the effects of factors such as the pressure, dry density, compression time under pressure, strain, and hydraulic gradient, permeability tests with saturated MBT waste were conducted by using a compression and permeability combined apparatus in an environmental geotechnical laboratory. The results showed that Darcy's law was applicable to the saturated MBT waste. The permeability coefficient was found to be inversely related to the pressure, dry density, compression time under pressure and strain. The logarithmic permeability coefficient and the variables (e.g., pressure) could largely be fitted to a linear function. Additionally, a prediction model for the permeability coefficient was established, and the permeability coefficient at different depths of MBT landfills was predicted. The results were then compared to previous studies on MSW and MBT waste to investigate the permeability mechanism.

Downregulation of miR-519a Predicts Poor Prognosis and Contributes to Tumor Progression in Gastric Cancer.

INTRODUCTION: MicroRNAs (miRNAs) have been demonstrated to be involved in the pathogenesis of various human cancers. However, the role of microRNA-519a (miR-519a) in gastric cancer (GC) remains unclear. This study aimed to investigate the clinical value and biological function of miR-519a in GC. METHODS: The expression of miR-519a in GC tissues and cell lines was estimated by quantitative real-time polymerase chain reaction. Survival analysis for GC patients was performed using the Kaplan-Meier method. Cox regression analysis was used to confirm the prognostic value of miR-519a. The biological function and potential targets of miR-519a in GC progression were assessed using cell experiments. RESULTS: In this study, we found that miR-519a was an important tumor suppressor with downregulated expression in GC tissues and cells compared with that in normal controls (all p < 0.05). MiR-519a expression was inversely correlated with differentiation, lymph node metastasis, and the TNM stage of patients. Decreased miR-519a expression was associated with the poor overall survival of GC patients (log-rank p = 0.002) and served as an independent prognostic biomarker for the patients. The in vitro analyses indicated that miR-519a overexpression in GC cells resulted in inhibited cell proliferation, migration, and invasion, and IGFBP1 was determined to be a direct target of miR-519a. CONCLUSION: All the data in the present study revealed that the downregulated expression of miR-519a predicts the poor prognosis of GC and is involved in the regulation of GC progression. We consider that miR-519a may be a candidate therapeutic target for GC treatment.

First-in-man study of Heartech® percutaneous left ventricular partitioning device for treatment of heart failure postmyocardial infarction.

OBJECTIVE: This first-in-man (FIM) study aimed to determine the safety and efficacy of the Heartech® left ventricular partitioning device (LVPD) in patients with chronic heart failure (HF) postmyocardial infarction. METHODS: Sixteen patients were enrolled from three cardiac intervention centers in China. All patients underwent percutaneous ventricular restoration (PVR) procedures with implantation of the Heartech® LVPD. Safety and immediate success rates were recorded. Major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause mortality, myocardial infarction, stroke, emergent or selective surgery or interventional therapy, renal failure requiring hemodialysis, and major bleeding were recorded. Efficacy features included functional status, echocardiographic characteristics, life quality characteristics including peak oxygen consumption of cardiopulmonary exercise testing (CPET), European five-dimensional health scale (EQ-5D), 6-min walk test (6MWT) at baseline and during follow-up (NCT02938637). RESULTS: The device success rate was 93.75% (15 successes in 16 patients) with 100% safety. During follow-up of 36 ± 4.5 days, no MACCEs were found. The left ventricular end-systolic volume index decreased significantly (LVESVi, 72.47 ± 22.77 mL/m2 vs. 50.13 ± 13.36 mL/m2 , p < .001) as did left ventricular end diastolic volume index (LVEDVi, 106.27 ± 28.01 mL/m2 vs. 83.20 ± 16.87 mL/m2 , p = .001). Left ventricular ejection fraction (LVEF, 32.47 ± 6.98% vs. 40.41 ± 6.15, p < .001), 6MWT (383.13 ± 108.70 vs. 453.47 ± 88.24, p < 0.001) and EQ-5D (65.93 ± 11.25 vs. 78.67 ± 8.35, p < .001) improved significantly. CONCLUSIONS: Heartech® LVPD appeared to be safe and effective for treatment of HF postmyocardial infarction.

Depletion of ß3-adrenergic receptor induces left ventricular diastolic dysfunction via potential regulation of energy metabolism and cardiac contraction.

Left ventricular diastolic dysfunction (LVDD) is a central perturbation in heart failure with preserved ejection fraction, and there are currently no effective remedies to improve LVDD in clinical practice. The ß3-adrenergic receptor (ADRB3) was reported to play protective effects on inhibiting myocardial fibrosis in response to hemodynamic stress. However, the effects of ADRB3 on LVDD and its underlying mechanisms are still undefined. In the current study, the role of ADRB3 in LVDD was identified in ADRB3-knockout mice. Echocardiography parameters showed that depletion of ADRB3 had little effect on cardiac systolic function but obviously led to cardiac diastolic dysfunction in vivo. Proteomics (including the global proteome, phosphorylated and acetylated proteome) and bioinformatics analysis (including GO analysis, KEGG pathway analysis, GO-Tree network, Pathway-Act network, and protein-protein interaction network) were performed on cardiac specimens of ADRB3-KO mice and wild-type mice. The results showed that the cardiac energy metabolism (especially the citrate cycle), actin cytoskeleton organization, and cardiac muscle contraction (related to mitogen-activated protein kinase, toll-like receptor, and ErbB signalling pathway) were potential core mechanisms underlying ADRB3-KO-induced LVDD. In addition, the protein-protein interaction network indicated that the core proteins associated with ADRB3-KO-induced LVDD were FGG, ALDH1A1, FGA, APOC3, SLC4A1, SERPINF2, HP, CTNNB1, and TKT. In conclusion, the absence of ADRB3 leads to LVDD, which is potentially associated with the regulation of cardiac energy metabolism, actin cytoskeleton organization, and cardiac muscle contraction.

The downregulation of miR-519a predicts poor prognosis and contributes to tumor progression in gastric cancer.

INTRODUCTION: MicroRNAs (miRNAs) have been demonstrated to be involved in the pathogenesis of various human cancers. However, the role of microRNA-519a (miR-519a) in gastric cancer (GC) remains unclear. This study aimed to investigate the clinical value and biological function of miR-519a in GC. METHODS: The expression of miR-519a in GC tissues and cell lines was estimated by quantitative real-time polymerase chain reaction (qRT-PCR). A survival analysis for GC patients was performed using the Kaplan-Meier method. A Cox regression analysis was used to confirm the prognostic value of miR-519a. The biological function and potential targets of miR-519a in GC progression were assessed using cell experiments. RESULTS: In this study, we found that miR-519a was an important tumor suppressor with downregulated expression in GC tissues and cells compared with the normal controls (all P < 0.05). MiR-519a expression was inversely correlated with differentiation, lymph node metastasis, and patients' TNM stages. Decreased miR-519a expression was associated with the poor overall survival of GC patients (log-rank P = 0.002) and served as an independent prognostic biomarker for the patients. The in vitro analyses indicated that miR-519a overexpression in GC cells resulted in inhibited cell proliferation, migration and invasion, and IGFBP1 was determined to be a direct target of miR-519a. CONCLUSION: All the data in the present study revealed that the downregulated expression of miR-519a predicts the poor prognosis of GC and is involved in the regulation of GC progression. We consider that miR-519a may be a candidate therapeutic target for GC treatment.

Influence of effective stress and dry density on the permeability of municipal solid waste.

A landfill is one of the main sites for disposal of municipal solid waste and the current landfill disposal system faces several problems. For instance, excessive leachate water is an important factor leading to landfill instability. Understanding the permeability characteristics of municipal solid waste is a relevant topic in the field of environmental geotechnical engineering. In this paper, the current research progress on permeability characteristics of municipal solid waste is discussed. A review of recent studies indicates that the research in this field is divided into two categories based on the experimental method employed: field tests and laboratory tests. This paper summarizes test methods, landfill locations, waste ages, dry densities and permeability coefficients across different studies that focus on permeability characteristics. Additionally, an experimental study on compressibility and permeability characteristics of fresh municipal solid waste under different effective stresses and compression times was carried out. Moreover, the relationships between the permeability coefficient and effective stress as well as dry density were obtained and a permeability prediction model was established. Finally, the experimental results from the existing literature and this paper were compared and the effects of effective stress and dry density on the permeability characteristics of municipal solid waste were summarized. This study provides the basis for analysis of leachate production in a landfill.

Activation of the Nkx2.5-Calr-p53 signaling pathway by hyperglycemia induces cardiac remodeling and dysfunction in adult zebrafish.

Hyperglycemia is an independent risk factor for diabetic cardiomyopathy in humans; however, the underlying mechanisms have not been thoroughly elucidated. Zebrafish (Danio rerio) was used in this study as a novel vertebrate model to explore the signaling pathways of human adult cardiomyopathy. Hyperglycemia was induced by alternately immersing adult zebrafish in a glucose solution or water. The hyperglycemic fish gradually exhibited some hallmarks of cardiomyopathy such as myocardial hypertrophy and apoptosis, myofibril loss, fetal gene reactivation, and severe arrhythmia. Echocardiography of the glucose-treated fish demonstrated diastolic dysfunction at an early stage and systolic dysfunction at a later stage, consistent with what is observed in diabetic patients. Enlarged hearts with decreased myocardial density, accompanied by decompensated cardiac function, indicated that apoptosis was critical in the pathological process. Significant upregulation of the expression of Nkx2.5 and its downstream targets calreticulin (Calr) and p53 was noted in the glucose-treated fish. High-glucose stimulation in vitro evoked marked apoptosis of primary cardiomyocytes, which was rescued by the p53 inhibitor pifithrin-µ. In vitro experiments were performed using compound treatment and genetically via cell infection. Genetically, knockout of Nkx2.5 induced decreased expression of Nkx2.5, Calr and p53 Upregulation of Calr resulted in increased p53 expression, whereas the level of Nkx2.5 remained unchanged. An adult zebrafish model of hyperglycemia-induced cardiomyopathy was successfully established. Hyperglycemia-induced myocardial apoptosis was mediated, at least in part, by activation of the Nkx2.5-Calr-p53 pathway in vivo, resulting in cardiac dysfunction and hyperglycemia-induced cardiomyopathy.