Efficient Lead Removal by Assembly of Bio-Derived Ellagate Framework, Which Enables Electrocatalytic Reduction of CO2 to Formate.

Lead (Pb) poisoning and CO2-induced global warming represent two exemplary environmental and energy issues threatening humanity. Various biomass-derived materials are reported to take up Pb and convert CO2 electrochemically into low-valent carbon species, but these works address the problems separately rather than settle the issues simultaneously. In this work, cheap, natural ellagic acid (EA) extracted from common plants is adopted to assemble a stable metal-organic framework (MOF), EA-Pb, by effective capture of Pb2+ ions in an aqueous medium (removal rate close to 99%). EA-Pb represents the first structurally well-defined Pb-based MOF showing selective electrocatalytic CO2-to-HCOO- conversion with Faradaic efficiency (FE) of 95.37% at -1.08 V versus RHE. The catalytic mechanism is studied by 13CO2 labeling, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and theoretical calculation. The use of EA-Pb as an electrocatalyst for CO2 reduction represents a 2-in-1 solution of converting detrimental wastes (Pb2+) as well as natural resources (EA) into wealth (electrocatalytic EA-Pb) for addressing the global warming issue.

Cost-Effectiveness Ratio Analysis of LBBaP Versus BVP in Heart Failure Patients With LBBB.

BACKGROUND: For the initial treatment strategy for patients with cardiac resynchronization therapy (CRT) indications, whether to choose left bundle branch area pacing (LBBaP) or biventricular pacing (BVP) remains controversial. We aimed to investigate the cost-effectiveness ratio (CER) of LBBaP and BVP in heart failure (HF) patients with left bundle branch block (LBBB). METHODS: This observational study included HF patients with LBBB who underwent successful LBBaP or BVP. The primary outcomes were echocardiographic response (left ventricular ejection fraction [LVEF] increase ≥5%), LVEF improvement, hospitalization costs, and CER (CER = cost/echocardiographic response rate). Secondary outcomes included other echocardiographic parameters, New York Heart Association (NYHA), N-terminal pro-B-type natriuretic peptide (NT-proBNP), pacemaker parameters, complications, ventricular arrhythmia (VA) events, HF hospitalization (HFH), and all-cause mortality. RESULTS: A total of 130 patients (85 LBBaP and 45 BVP) were included (65.6 ± 10.0 years, 70.77% men). The median follow-up period was 16(12,30), months. Compared with BVP, the LBBaP group showed a greater increase in LVEF (20.2% ± 11.8% vs. 10.5% ± 13.9%; p < 0.001), higher echocardiographic response rate (86.1% vs. 57.8%; p < 0.001), and lower hospitalization costs [$9707.7 (7751.2, 18,088.5) vs. $20,046.1 (18,840.1, 22,447.3); p < 0.0001]. The CER was 112.7 and 346.8 in LBBaP and BVP, respectively. The incremental cost-effectiveness ratio (ICER = △cost/△echocardiographic response rate) was $-365.3/per 1% increase in effectiveness. LBBaP improved cardiac function more significantly than BVP. There were no significant differences in clinical outcomes. CONCLUSIONS: LBBaP-CRT is more cost-effective than BVP, offering greater LVEF improvement, higher echocardiographic response rates, lower hospitalization costs, and more significantly improved cardiac function. These findings need large randomized clinical trials for further confirmation.

Predictors of functional mitral regurgitation improvement in patients with left bundle branch block treated with left bundle branch area pacing.

BACKGROUND: Functional mitral regurgitation (FMR) and its severity are associated with adverse outcomes in heart failure patients. This study aims to analyze the predictors of FMR improvement after successful left bundle branch area pacing (LBBAP) in patients with LVEF < 50% and complete left bundle branch block (CLBBB). METHODS: Consecutive patients with LVEF < 50% and CLBBB who underwent successful LBBAP from July 2018 to July 2023 were retrospectively identified. Significant MR was defined as regurgitation of moderate severity or greater. Patients with significant FMR were included in the analysis. FMR improvement (FMRI) was defined as a reduction of at least one grade in regurgitation severity compared to baseline at 3 months or longer follow-up. RESULTS: Among the 81 identified patients, 42 patients with significant FMR preoperatively were included. After LBBAP, QRS duration significantly shortened from 170.6 ± 18.8 ms to 114.5 ± 20.2 ms (p < .001). Significant FMR improves in approximately 76.2%, and the patients were divided into an FMRI group (n = 32) and a non-FMRI group (n = 10). Univariate analysis showed that absence of persistent atrial fibrillation, typical CLBBB, and left atrium diameter at baseline were associated with improvement of FMR after LBBAP. Of these variables, only absence of persistent atrial fibrillation remains an independent predictor in the multivariate model (OR 12.436, p = .009). CONCLUSION: LBBAP is able to improve FMR in heart failure patients who had CLBBB with LVEF < 50%. Meanwhile, the absence of persistent atrial fibrillation is an independent predictor of FMR improvement.

Beyond silence: evolving ultrasound strategies in the battle against cardiovascular thrombotic challenges.

Cardiovascular thrombotic events have long been a perplexing factor in clinical settings, influencing patient prognoses significantly. Ultrasound-mediated acoustic therapy, an innovative thrombolytic treatment method known for its high efficiency, non-invasiveness, safety, and convenience, has demonstrated promising potential for clinical applications and has gradually become a focal point in cardiovascular thrombotic disease research. The current challenge lies in the technical complexities of preparing ultrasound-responsive carriers with thrombus-targeting capabilities and high thrombolytic efficiency. Additionally, optimizing the corresponding acoustic treatment mode is crucial to markedly enhance the thrombolytic effectiveness of ultrasound-mediated acoustic therapy. In light of the current status, this article provides a comprehensive review of the research progress in innovative ultrasound-mediated acoustic therapy for cardiovascular thrombotic diseases. It explores the impact of technical methods, therapeutic mechanisms, and influencing factors on the thrombolytic efficiency and clinical potential of ultrasound-mediated acoustic therapy. The review places particular emphasis on identifying solutions and key considerations in addressing the challenges associated with this cutting-edge therapeutic approach.

Dual-mode nanoprobe strategy integrating ultrasound and near-infrared light for targeted and synergistic arterial thrombolysis.

Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis.

Molecular hydrogen promotes retinal vascular regeneration and attenuates neovascularization and neuroglial dysfunction in oxygen-induced retinopathy mice.

BACKGROUND: Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice. METHODS: In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining. RESULTS: Our results indicate that 3-4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression. CONCLUSIONS: Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways.

Ultrasound-mediated cardiovascular thrombolysis: from Sonothrombolysis to Sonoperfusion.

The incidence of coronary artery disease has been increasing in recent years, with acute myocardial infarction as its most severe onset. The major aim for clinical treatment is to restore myocardial blood supply with the recanalization of coronary circulation as early as possible, while the still existed issue of microcirculation thromboembolism has become a serious obstacle. Thus, thrombus elimination in coronary microcirculation is crucial and essential to improve the treatment outcome of acute myocardial infarction. In recent years, from sonothrombolysis to sonoperfusion, ultrasound-mediated cardiovascular thrombolysis can effectively solve the problem of vascular thromboembolism, including microcirculation thromboembolism, and the treatment method is expected to obtain satisfied thrombolytic treatment effect with microthrombus elimination in coronary microvessels and function recovery of terminal microcirculation, which has potential clinical value for the establishment of novel treatment for coronary thromboembolism. Therefore, this paper reviews ultrasound-mediated cardiovascular thrombolysis including sonothrombolysis and sonoperfusion for the application exploration in the treatment of coronary artery thromboembolism, the mechanism of action, and its research progress.

MicroRNA-204-5p Attenuates Oxidative Stress, Apoptosis and Inflammation by Targeting TXNIP in Diabetic Cataract.

Diabetic cataract (DC) is a major cause of blindness in diabetic patients and it is characterized by early onset and rapid progression. MiR-204-5p was previously identified as one of the top five down-regulated miRNAs in human DC lens tissues. We aimed to determine the expression of miR-204-5p in human lens epithelial cells (HLECs) and explore its effects and mechanisms in regulating the progression of DC. The expression of miR-204-5p in the anterior capsules of DC patients and HLECs was examined by RT-qPCR. Bioinformatics tools were then used to identify the potential target of miR-204-5p. The relationship between miR-204-5p and the target gene was confirmed through a dual luciferase reporter assay. Additionally, the regulatory mechanism of oxidative stress, apoptosis, and inflammation in DC was investigated by overexpressing miR-204-5p using miR-204-5p agomir. The expression of miR-204-5p was downregulated in the anterior capsules of DC patients and HLECs. Overexpression of miR-204-5p reduced ROS levels, pro-apoptosis genes (Bid, Bax, caspase-3), and IL-1ß production in HG-treated HLECs. TXNIP was the direct target of miR-204-5p by dual luciferase reporter assay. Therefore, this study demonstrated that miR-204-5p effectively reduced oxidative damage, apoptosis, and inflammation in HLECs under HG conditions by targeting TXNIP. Targeting miR-204-5p could be a promising therapeutic strategy for the potential treatment of DC.

Study on susceptibility differences of Tetranychus cinnabarinus (Boisduval) males and females to acaricides.

The carmine spider mite, Tetranychus cinnabarinus (Boisduval), is an important agricultural arthropod pest. This study investigated acaricide susceptibility differences between sexes to determine the biochemical mechanisms potentially involved in these differences. The susceptibility of females and males to seven acaricides (pyridaben, cyflumetofen, abamectin, chlorpyrifos, propargite, profenofos and fenpropathrin) was compared with laboratory bioassays. Males were more susceptible than females for each acaricide. Differences in the lethal concentration 50 % (LC50) values between the sexes were observed to range from 2.04-fold to 6.05-fold. The surface area was markedly greater for females than males (by 1.87-fold) and the weight was significantly greater for females compared to males (by 4.67-fold). The specific surface area of male was 2.61-fold higher than that of female. There were no differences in the cuticle structure, whereas the thickness of females was 1.63-fold than that of males. The penetration rate of males was statistically significantly higher than that of females, both in pyridaben and cyflumetofen. Synergism experiments and biochemical assays suggested the involvement of the three detoxification enzyme systems in the sexual susceptibility of T. cinnabarinus. The activities of cytochrome P450 monooxygenases (P450s) (p < 0.01), glutathione-S-transferase (GSTs) (p < 0.05) and carboxylesterase (CarEs) (p < 0.05) in females were significantly higher than that in males. The results reveal that the individual size (specific surface area), cuticle thickness, and detoxification enzyme activity were involved in the sexual susceptibility to acaricides of T. cinnabarinus.

Utilizing Metal-Thiocatecholate Functionalized UiO-66 Framework for Photocatalytic Hydrogen Evolution Reaction.

Exploiting clean energy is essential for sustainable development and sunlight-driven photocatalytic water splitting represents one of the most promising approaches toward this goal. Metal-organic frameworks (MOFs) are competent photocatalysts owing to their tailorable functionality, well-defined structure, and high porosity. Yet, the introduction of the unambiguous metal-centered active site into MOFs is still challenging since framework motifs capable of anchoring metal ions firmly are lacking. Herein, the assembly using 1,4-dicarboxylbenzene-2,3-dithiol (H2 dcbdt) and Zr-Oxo clusters to give a thiol-functionalized UiO-66 type framework, UiO-66-dcbdt, is reported. The thiocatechols on the struts are allowed to capture transition metal (TM) ions to generate UiO-66-dcbdt-M (M  = Fe, Ni, Cu) with unambiguous metal-thiocatecholate moieties for photocatalytic hydrogen evolution reaction (HER). UiO-66-dcbdt-Cu is found the best catalyst exhibiting an HER rate of 4.18 mmol g-1  h-1  upon irradiation with photosensitizing Ru-polypyridyl complex. To skip the use of the external sensitizer, UiO-66-dcbdt-Cu is heterojunctioned with titanium dioxide (TiO2 ) and achieves an HER rate of 12.63 mmol g-1  h-1  (32.3 times that of primitive TiO2 ). This work represents the first example of MOF assembly employing H2 dcbdt as the mere linker followed by chelation with TM ions and undoubtedly fuels the rational design of MOF photocatalysts bearing well-defined active sites.

Automatic reorientation by deep learning to generate short-axis SPECT myocardial perfusion images.

BACKGROUND: Single photon emission computed tomography (SPECT) myocardial perfusion images (MPI) can be displayed both in traditional short-axis (SA) cardiac planes and polar maps for interpretation and quantification. It is essential to reorient the reconstructed transaxial SPECT MPI into standard SA slices. This study is aimed to develop a deep-learning-based approach for automatic reorientation of MPI. METHODS: A total of 254 patients were enrolled, including 226 stress SPECT MPIs and 247 rest SPECT MPIs. Fivefold cross-validation with 180 stress and 201 rest MPIs was used for training and internal validation; the remaining images were used for testing. The rigid transformation parameters (translation and rotation) from manual reorientation were annotated by an experienced nuclear cardiologist and used as the reference standard. A convolutional neural network (CNN) was designed to predict the transformation parameters. Then, the derived transform was applied to the grid generator and sampler in spatial transformer network (STN) to generate the reoriented image. A loss function containing mean absolute errors for translation and mean square errors for rotation was employed. A three-stage optimization strategy was adopted for model optimization: (1) optimize the translation parameters while fixing the rotation parameters; (2) optimize rotation parameters while fixing the translation parameters; (3) optimize both translation and rotation parameters together. RESULTS: In the test set, the Spearman determination coefficients of the translation distances and rotation angles between the model prediction and the reference standard were 0.993 in X axis, 0.992 in Y axis, 0.994 in Z axis, 0.987 along X axis, 0.990 along Y axis and 0.996 along Z axis, respectively. For the 46 stress MPIs in the test set, the Spearman determination coefficients were 0.858 in percentage of profusion defect (PPD) and 0.858 in summed stress score (SSS); for the 46 rest MPIs in the test set, the Spearman determination coefficients were 0.9 in PPD and 0.9 in summed rest score (SRS). CONCLUSIONS: Our deep learning-based LV reorientation method is able to accurately generate the SA images. Technical validations and subsequent evaluations of measured clinical parameters show that it has great promise for clinical use.

Ni(II)-Pyrazolate Framework Bearing a Metalated Schiff-Base Moiety for Electrocatalytic Hydrogen Evolution.

A robust and porous Ni-based metal-organic framework (MOF), NiL1, was assembled from Ni(II) ions and a dipyrazolate linker (L12-). A Ni(II)-anchored MOF catalyst Ni@NiL1-Sal has been successfully prepared by post-synthetic modification (PSM) condensation between NiL1 with salicylaldehyde, followed by chelation of Ni(II) ions by salicylaldimine as a secondary active site. Ni@NiL1-Sal with carbon black was found to exhibit enhanced electrocatalytic hydrogen evolution reaction (HER) performance (the smallest overpotential, 384 mV, and Tafel slope, 87 mV dec-1) when compared with primitive NiL1 and NiL1-Sal. Such improvement in HER highlights the creation of unambiguous secondary active sites as an avenue to the rational design of a functional MOF-based electrocatalyst.

Left Bundle Branch Pacing for Bradycardia in Non-obstructive Hypertrophic Cardiomyopathy Patients: Feasibility, Safety, and Effect.

PURPOSE: Left bundle branch pacing (LBBP) is as an innovative physiological pacing approach. The research on LBBP in non-obstructive hypertrophic cardiomyopathy (NOHCM) patients is scarce. This study aimed to assess the feasibility, safety, and effect of LBBP in bradycardia NOHCM patients with permanent pacemaker (PPM) implantation indication. METHODS: Thirteen consecutive patients with NOHCM who received LBBP were retrospectively enrolled as a hypertrophic cardiomyopathy (HCM) group. Following 1:3 matching, 39 patients without HCM were randomly matched as a control group. Echocardiographic index and pacing parameters were collected. RESULTS: The successful LBBP was achieved in 96.2% of all cases (50/52), and the success rate of the HCM group was 92.3% (12/13). In the HCM group, the paced QRS duration (from the pacing stimulus to QRS end) was 145.6±20.8 ms. The stimulus to left ventricular activation time (s-LVAT) was 87.4±15.2 ms. In the control group, the paced QRS duration was 139.4±17.2 ms, and the s-LVAT was 79.9±14.1 ms. During the implantation, R-wave sensing and the pacing threshold of the HCM group were significantly higher than the control group (20.2±10.5 vs 12.5±5.9 mV, P < 0.05; 0.8±0.3 vs 0.6±0.2V/0.4 ms, P < 0.05). In addition, the fluoroscopic duration and procedural duration were longer in the HCM group (14.8±8.3 vs 10.3±6.6min, P = 0.07; 131.8±50.5 vs 101.4±41.6 min, P < 0.05). The lead insertion depth was 15±2 mm in the HCM group, and no procedure-related complications occurred. During the 12-month follow-up, pacing parameters remained stable and were of no significance in the two groups. The cardiac function did not deteriorate, and the left ventricular outflow tract gradient (LVOTG) did not increase in the follow-up. CONCLUSION: LBBP might be feasible and safe for NOHCM patients with conventional bradycardia pacing indication, and there is no deterioration in cardiac function and LVOTG of patients with NOHCM.

Autologous non-invasively derived stem cells mitochondria transfer shows therapeutic advantages in human embryo quality rescue.

BACKGROUND: The decline in the quantity and quality of mitochondria are closely associated with infertility, particularly in advanced maternal age. Transferring autologous mitochondria into the oocytes of infertile females represents an innovative and viable strategy for treating infertility, with no concerns regarding ethical considerations. As the donor cells of mitochondria, stem cells have biological advantages but research and evidence in this area are quite scarce. METHODS: To screen out suitable human autologous ooplasmic mitochondrial donor cells, we performed comprehensive assessment of mitochondrial physiology, function and metabolic capacity on a varity of autologous adipose, marrow, and urine-derived mesenchymal stromal cells (ADSC, BMSC and USC) and ovarian germline granulosa cells (GC). Further, to explore the biosafety, effect and mechanism of stem cell-derived mitochondria transfer on human early embryo development, randomized in-vitro basic studies were performed in both of the young and aged oocytes from infertile females. RESULTS: Compared with other types of mesenchymal stromal cells, USC demonstrated a non-fused spherical mitochondrial morphology and low oxidative stress status which resembled the oocyte stage. Moreover, USC mitochondrial content, activity and function were all higher than other cell types and less affected by age, and it also exhibited a biphasic metabolic pattern similar to the pre-implantation stage of embryonic development. After the biosafety identification of the USC mitochondrial genome, early embryos after USC mitochondrial transfer showed improvements in mitochondrial content, activity, and cytoplasmic Ca2+ levels. Further, aging embryos also showed improvements in embryonic morphological indicators, euploidy rates, and oxidative stress status. CONCLUSION: Autologous non-invasively derived USC mitochondria transfer may be an effective strategy to improve embryonic development and metabolism, especially in infertile females with advanced age or repeated pregnancy failure. It provides evidence and possibility for the autologous treatment of infertile females without invasive and ethical concerns.

The MFF-SIRT1/3 axis, regulated by miR-340-5p, restores mitochondrial homeostasis of hypoxia-induced pulmonary artery smooth muscle cells.

Mitochondrial dynamics and quality control play a central role in the maintenance of the proliferation-apoptosis balance, which is closely related to the progression of pulmonary arterial hypertension (PAH). However, the exact mechanism of this balance remains unknown. Pulmonary artery smooth muscle cells (PASMCs) were cultured in hypoxia condition for constructing a PAH model in vitro. The expression of genes and proteins were determined by qRT-PCR and western bolt assays. Cell proliferation-apoptosis balance were tested by MTT, EdU and TUNEL assays. The mitochondrial functions were assessed by flow cytometry, JC-1, Mito tracker red staining, and corresponding kits. Besides, the molecular interaction was validated by dual-luciferase reporter assay. MFF was overexpressed in hypoxia-treated PAMSCs. Knockdown of MFF significantly repressed the excessive proliferation but enhanced cell apoptosis in hypoxia-treated PAMSCs. Moreover, MFF silencing improved mitochondrial function of hypoxia-treated PAMSCs by increasing ATP production and decreasing ROS release and mitochondrial fission. Mechanistically, MFF was a directly target of miR-340-5p, and could negatively regulate SIRT1/3 expression. Subsequently, functional rescue assays showed that the biological effects of MFF in hypoxia-treated PAMSCs were negatively regulated by miR-340-5p and depended on the regulation on SIRT1/3 pathway. These results provided evidences that miR-340-5p regulated MFF-SIRT1/3 axis to improve mitochondrial homeostasis and proliferation-apoptosis imbalance of hypoxia-treated PAMSCs, which provided a theoretical basis for the prevention and treatment of PAH.

Renal denervation ameliorates cardiac metabolic remodeling in diabetic cardiomyopathy rats by suppressing renal SGLT2 expression.

This study aimed to investigate the effects of renal denervation (RDN) on diabetic cardiomyopathy (DCM) and explore the related mechanisms. Male Sprague-Dawley rats were fed high-fat chow and injected with low-dose streptozotocin to establish a DCM model. Six rats served as controls. The surviving rats were divided into three groups: control group, DCM group and DCM + RDN group. RDN surgery was performed in the fifth week. At the end of the experiment, all rats were subjected to 18F-FDG PET/CT and metabolic cage studies. Cardiac function and structure were evaluated by echocardiography and histology. Myocardial substrate metabolism and mitochondrial function were assessed by multiple methods. In the 13th week, the DCM rats exhibited cardiac hypertrophy and interstitial fibrosis accompanied by diastolic dysfunction. RDN ameliorated DCM-induced cardiac dysfunction (E/A ratio: RDN 1.07 ± 0.18 vs. DCM 0.93 ± 0.12, P < 0.05; E/E' ratio: RDN 10.74 ± 2.48 vs. DCM 13.25 ± 1.99, P < 0.05) and pathological remodeling (collagen volume fraction: RDN 5.05 ± 2.05% vs. DCM 10.62 ± 2.68%, P < 0.05). Abnormal myocardial metabolism in DCM rats was characterized by suppressed glucose metabolism and elevated lipid metabolism. RDN increased myocardial glucose uptake and oxidation while reducing the absorption and utilization of fatty acids. Meanwhile, DCM decreased mitochondrial ATP content, depolarized the membrane potential and inhibited the activity of respiratory chain complexes, but RDN attenuated this mitochondrial damage (ATP: RDN 30.98 ± 7.33 µmol/gprot vs. DCM 22.89 ± 5.90 µmol/gprot, P < 0.05; complexes I, III and IV activity: RDN vs. DCM, P < 0.05). Furthermore, both SGLT2 inhibitor and the combination treatment produced similar effects as RDN alone. Thus, RDN prevented DCM-induced cardiac dysfunction and pathological remodeling, which is related to the improvement of metabolic disorders and mitochondrial dysfunction.

Clinical benefit of systolic blood pressure within the target range among patients with or without diabetes mellitus: a propensity score-matched analysis of two randomized clinical trials.

BACKGROUND: Recent guidelines recommended a systolic blood pressure (SBP) target of < 130 mmHg for patients with or without diabetes but without providing a lower bound. Our study aimed to explore whether additional clinical benefits remain at achieved blood pressure (BP) levels below the recommended target. METHODS: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) among the non-diabetic population and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial among diabetic subjects. We used the propensity score method to match patients from the intensive BP group to those from the standard group in each trial. Individuals with different achieved BP levels from the intensive BP group were used as "reference." For each stratum, the trial-specific primary outcome (i.e., composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death for SPRINT; non-fatal MI, non-fatal stroke, or cardiovascular death for ACCORD-BP) was compared by Cox regression. RESULTS: A non-linear association was observed between the mean achieved BP and incidence of composite cardiovascular events, regardless of treatment allocation. The significant treatment benefit for primary outcome remained at SBP 110-120 mmHg (hazard ratio, 0.59 [95% CI, 0.46, 0.76] for SPRINT; 0.67 [0.52, 0.88] for ACCORD-BP) and SBP 120-130 mmHg for SPRINT (0.47 [0.34, 0.63]) but not for ACCORD-BP (0.93 [0.70, 1.23]). The results were similar for the secondary outcomes including all-cause mortality, cardiovascular mortality, MI, stroke, and HF. Intensive BP treatment benefits existed among patients maintaining a diastolic BP of 60-70 mmHg but were less distinct. CONCLUSIONS: The treatment benefit persists at as low as SBP 110-120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality.

Interventricular septum angle obtained from cardiac computed tomography for origin differentiation of outflow tract ventricular arrhythmia between left and right.

AIMS: Our objective was to explore whether the accuracy of the transitional zone index (TZI) for outflow tract ventricular arrhythmias (OT-VAs) origin is affected by cardiac rotation and the additive value of interventricular septum angle (IVSa) obtained from coronary computed tomography angiography (CCTA). METHODS: Standard 12-lead ECGs of OT-VAs with inferior axis in consecutive patients undergoing both CCTA examination and successful ablation were retrospectively analyzed. The IVSa was defined as an angle between the long axis of IVS and sagittal axis of the body from CCTA. RESULTS: 64 patients (31 men; mean age 54.2 ± 11.6 years) were enrolled. The OT-VAs exhibited right ventricular outflow tract origin in 46 (71.9%) patients and 36 (78.3%) were diagnosed correctly by TZI. The left ventricular outflow tract origin OT-VAs was observed in 18 (28.1%) patients and 16 (88.9%) were diagnosed correctly by TZI. The patients were then divided into TZI correct group (n = 52) and TZI incorrect group (n = 12). In the TZI incorrect group, 11/12 (91.7%) cases were R/S transition in lead V3 with the TZ score during premature ventricular contractions [2.8(2.5-3.4)], and the TZI between -1.5 and 0. The IVSa was significantly larger in the TZI incorrect group than correct group (52.0 ± 6.9° vs. 39.0 ± 6.1°; p < .0001). The IVSa ≥46° predicted TZI incorrect with 92% sensitivity, 94% specificity, and 94% accuracy. CONCLUSION: The IVSa is a novel cardiac rotation index that reliably improves TZI to differentiate the OT-VAs origin, especially for the OT-VAs with lead V3 R/S transition.

Were economic evaluations well reported for the newly listed oncology drugs in China's national reimbursement drug list.

PURPOSE: To assess the reporting quality of published economic evaluations of the negotiated oncology drugs listed for China's 2020 National Reimbursement Drug List (NRDL). METHODS: A comprehensive search was conducted to identify economic evaluation studies of negotiated oncology drugs listed in China's 2020 NRDL using the PubMed/MEDLINE, Embase, Web of Science, CNKI, SinoMed, and WanFang Database up to March 31, 2021. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist scored the reporting quality between 0 and 100. A linear regression analysis was employed to examine the influence of various characteristics on the reporting quality scores. RESULTS: Eighty papers were included in the study, with the majority published during the past decade. Furthermore, more than half of the articles (57.5%, or 46 out of 80) were written in English. The average CHEERS score was 74.63 ± 12.75 and ranged from 43.48 to 93.75. The most inadequately reported items included choice of model, characterization of heterogeneity, and discussion, as well as currency, price date and conversion. Higher scores were associated with articles published from 2019 to 2021 and English publications. CONCLUSION: The economic evaluation studies of negotiated oncology drugs listed in 2020 NRDL had moderate reporting quality. The Chinese economic evaluation publications could improve the reporting quality if the CHEERS checklist is consistently implemented. Also, the Chinese journals maybe explore introducing a reporting standard for economic evaluations.

Neuronal nitric oxide synthase in dorsal raphe nucleus mediates PTSD-like behaviors induced by single-prolonged stress through inhibiting serotonergic neurons activity.

The pathogenesis of post-traumatic stress disorder (PTSD) remains largely unclear. A large body of evidence suggests that the abnormal level of serotonin (5-HT) is closely related to the onset of PTSD. Several reports reveal that nitric oxide (NO) affects extracellular 5-HT levels in various brain regions, but no consistent direction of change was found and the underlying mechanisms remain unknown. The most of serotonergic neurons in dorsal raphe nucleus (DRN), a major source of serotonergic input to the forebrain, co-expresses neuronal nitric oxide synthase (nNOS), a synthase derived nitric oxide (NO) in the central nervous system. Here, we found that the excessive expression of nNOS and thereby the high concentration of NO followed by single-prolonged stress (SPS) caused suppression of the activity of DRN 5-HT neurons, inducing PTSD-like phenotype including increased anxiety-like behaviors, enhanced contextual fear memory, and fear generalization. Our study uncovered an important role of DRN nNOS-NO pathway in the pathology of PTSD, which may contribute to new understanding of the molecular mechanism of PTSD.