Desmoplakin and clinical manifestations of desmoplakin cardiomyopathy / 中华医学杂志(英文版)

Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.

Feasibility and safety of new simplified left bundle branch area pacing via nine-partition method / 中华心血管病杂志

Objective: To investigate the efficacy and safety of left bundle branch area pacing (LBBaP) with the new simplified approach (nine-partition method). Methods: A total of 118 patients with clinical indications and received pacemaker implantation from December 1, 2018 to December 31, 2019 in Beijing Anzhen Hospital were enrolled. LBBaP was performed with the nine-partition method (in the right anterior oblique 30° position, the ventriculogram was divided into nine partitions and the initial implant sites were located in the lower base 1/3 partitions). In X-ray image, the 3830 lead is located in the left bundle branch area, the unipolar pacing QRS wave is in the form of right bundle branch block, and the peak time from stimulation to left ventricular activation<90 ms is defined as successful operation. The clinical characters, such as the methods of venipuncture, electrode parameters, operation duration, fluoroscopy duration, the peak time from stimulation to left ventricular, pacemaker types, surgical success rate, complications, and immediate postoperative ECG parameters were collected. The patients were followed up after the operation, and the electrode parameters and postoperative complications were recorded. Results: This study is a retrospective study. There were 62 (52.5%) male patients in this cohort, the average age was (65.9±13.4) years old,and there were 49(41.5%) sick sinus syndrome, 6(5.1%) abnormal sinus node and atrioventricular node simultaneously, 63(53.4%) atrioventricular block, 26(22.0%) atrial fibrillation, 20(16.9%) cardiomyopathy; the baseline duration of QRS was (109.21±39.03) ms. Successful LBBaP was achieved in 109 patients with"nine-partition method"and the success rate was 92.4%; 104 patients (95.5%) were axillary vein puncture, 5 (4.6%) were subclavian vein puncture; the operation duration was (80.3±23.0) min, the fluoroscopy duration was (12.29±5.13) min; the QRS duration after LBBaP was (116.36±18.11) ms. The threshold of the left bundle branch (LBB) lead was (0.92±0.63) V, the R wave amplitude was (10.60±5.04) mV and the impedance was (798.71±194.90) Ω. In 1 V pacing, the peak time from stimulation to left ventricular activation was (67.91±12.15) ms, and in 5 V pacing was (67.52±12.45) ms; 1 case (0.9%) with a single-chamber pacemaker implanted, 106 cases (97.3%) with dual-chamber pacemaker and 2 cases (1.8%) with three-chamber pacemakers. There were no hematomas, pneumothorax, hemothorax, electrode dislocation, infection, and capsular hemorrhage and other serious surgery-related complications during the operation. A total of 97 patients (89.0%) were followed up for (6.21±2.90) months. The electrode parameters of all patients were stable and no complications observed. Conclusions: The LBBaP with nine-partition method is a simple, safe and effective physiological pacing approach. However, its long-term effect still needs to be further verified.

A simple strategy for delivery of carbon monoxide against septic lung injury / 药学学报

Carbon monoxide (CO) is an important chemical gas messenger molecule in the body with anti-inflammatory activity. As an active substance in gaseous state, the method for its safe and effective delivery towards the lesion sites remains to be established. Based on the natural affinity of carbon monoxide to hemoglobin, a main component of red blood cells (RBCs), this study proposes a carbon monoxide-red blood cell (CO-RBC) composite system, and tested its therapeutic effect against lung injury in an animal model. The mouse model of septic lung injury was adopted, and the carbon monoxide release molecule (CORM-2) was used as a positive control. CO-RBC system was characterized by CO release, stability, toxicity and in vivo lung targeting. The expression of intercellular adhesion molecule (ICAM-1) and pulmonary surfactant protein-A (SP-A) were evaluated in the animal model and the therapeutic effect of CO-RBC system for sepsis was measured by inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as survival time of mice and pathological changes of the lung. Our results show that CO-RBC system exhibited satisfactory stability with negligible CO release during 48 h storage under nitrogen protection, while the CO release was about 70% within 12 h under physiological condition, in contrast to CO burst release from CORM-2. The CO-RBC system showed no significant toxicity in the animal model, and in vivo fluorescence imaging results showed effective accumulation in the lungs, supporting its lung targeting effects. The secretion of TNF-α and IL-6 in the CO-RBC group was significantly lower than that in other groups, the degree of pulmonary interstitial edema was relieved, the white blood cell infiltration was decreased, and the survival rate was significantly improved. Therefore, the CO-RBC system has a significant inhibitory effect on the pulmonary inflammatory response in septic mice compared with CORM-2. This system provides a new hope for therapeutic treatment of sepsis.

Recent approaches to His-Purkinje system pacing / 中华医学杂志(英文版)

OBJECTIVE@#Physiologic cardiac pacing is a novel technique which has been largely popularized in recent decades. His bundle pacing (HBP) has been long considered the most physiologic pacing method; however, with the widespread implementation of this method, its disadvantages have become apparent. In this context, left bundle branch pacing (LBBP)-directly engaged in the His-Purkinje system-has been foreseen as the best pacing method to mimic physiologic activation patterns. This review aimed to summarize recent approaches to physiologic cardiac pacing.@*DATA SOURCES@#This review included fully peer reviewed publications up to July 2018, found in the PubMed database using the keywords "His bundle branch pacing," "right ventricular pacing," and "physiologic pacing."@*STUDY SELECTION@#All selected articles were in English, with no restriction on study design.@*RESULTS@#The HBP has been studied worldwide, and is currently considered the most physiologic pacing method. However, it has disadvantages, such as high pacing threshold, unsatisfactory sensing and long procedure times, among others. Although LBBP is theoretically superior to HBP, the clinical relevance of this difference remains under debate, as few large randomized clinical trials with LBBP have been published.@*CONCLUSIONS@#Although HBP indeed appears to be the most physiologic pacing method, it has certain shortcomings, such as high pacing threshold, difficult implantation due to specific anatomic features, and others. Further studies are required to clarify the clinical significance of LBBP.

A preliminary study on the biomimetic drug delivery system targeting atherosclerotic lesions / 药学学报

Based on the natural affinity between macrophages and atherosclerotic lesions, we made a novel macrophage membrane-coated polylactic acid-glycolic acid copolymer (PLGA) nanoparticle (MPLNPs), and examined its ability targeting atherosclerotic lesions. PLGA nanoparticle (PLGANPs) were prepared by precipitation and MPLNPs were prepared by membrane extrusion. Their morphology, particle size and retainment of functional proteins were characterized. Their targeting capabilities were investigated with cell uptake assay in vitro and fluorescence imaging in vivo. The results showed that MPLNPs were spherical, with obvious core/shell structure, the average particle size was (167 ±6.12) nm, and integrin α4β1 was retained on the surface. Vascular cell adhesion molecule 1 (VCAM-1) receptor was highly expressed in the LPS (lipopolysaccharides)-HUVEC (human umbilical vein endothelial cells) and atherosclerotic lesions in ApoE-/- mouse model, and the nanoparticles could effectively recognize the VCAM-1 receptor and had good targeting properties in vitro and in vivo. The results suggest that the cell membrane biomimetic nano-carrier may provide a new approach for the targeting strategy in the treatment of atherosclerosis and related diseases.