The clinical use of remote parameter testing during cardiac implantable electronic devices implantation procedures: a single center, randomized, open-label, non-inferiority trial.

Background: A novel non-contact system for remote parameter testing and reprogramming offers an alternative method for assessing device parameters during cardiac implantable electronic devices (CIEDs) implantation without the need for physical contact with the manufacturer's clinical service technician. The safety and feasibility of using this system in CIEDs implantation procedures remains to be determined. Objective: Evaluate the safety and feasibility of remote parameter testing in CIEDs implantation procedures. Methods: A single center, randomized, open-label, non-inferiority trial (ChiCTR2200057587) was conducted to compare the two approaches for interrogating CIEDs during implantation procedures: routine interrogation performed by on-site technicians or remote interrogation performed by technicians using the 5G-Cloud Technology Platform. Patients aged ≥18 years and elected to receive CIEDs were eligible for inclusion. The primary endpoint was the completion rate of the parameter test. Safety and efficiency were evaluated in all randomly assigned participants. Results: A total of 480 patients were finally enrolled and were randomly assigned to routine group (n = 240) or remote group (n = 240). The primary endpoint was achieved by 100% in both groups (P = 0.0060 for noninferiority). The parameters of sensing, threshold, and impedance regarding the right atrium, right ventricle, and left ventricle had no statistical significance between the two groups (P > 0.05). Procedure time, parameter testing time, and both duration and dose of x-ray irradiation were not significantly different between the two groups (P > 0.05). Shut-open door frequency was significantly higher in the routine group than the remote group [6.00 (4.00, 8.00) vs. 0, P < 0.0001]. Notably, no clinical or technical complications were observed in the remote group. Conclusions: Remote parameter testing is safe and feasible across various devices implantation procedures. The utilization of remote parameter testing and reprogramming could represent an innovative approach to improve healthcare accessibility and unlock the full potential of secondary centers in managing CIEDs. The Registration Identification: ChiCTR2200057587.

Simulated microgravity attenuates skin wound healing by inhibiting dermal fibroblast migration via F-actin/YAP signaling pathway.

Skin and its cell components continuously subject to extrinsic and intrinsic mechanical forces and are mechanical sensitive. Disturbed mechanical homeostasis may lead to changes in skin functions. Gravity is the integral mechanical force on the earth, however, how gravity contributes to the maintenance of skin function and how microgravity in space affects the wound healing are poorly understood. Here, using microgravity analogs, we show that simulated microgravity (SMG) inhibits the healing of cutaneous wound and the accumulation of dermal fibroblasts in the wound bed. In vitro, SMG inhibits the migration of human foreskin fibroblast cells (HFF-1), and decreases the F-actin polymerization and YAP (yes-associated protein) activity. The SMG-inhibited migration can be recovered by activating YAP or F-actin polymerization using lysophosphatidic acid (LPA) or jasplakinolide (Jasp), suggesting the involvement of F-actin/YAP signaling pathway in this process. In SMG rats, LPA treatment improves the cutaneous healing with increased dermal fibroblasts in the wound bed. Together, our results demonstrate that SMG attenuates the cutaneous wound healing by inhibiting dermal fibroblast migration, and propose the crucial role of F-actin/YAP mechano-transduction in the maintenance of skin homeostasis under normal gravity, and YAP as a possible therapeutic target for the skin care of astronauts in space.

YAP Inhibition Alleviates Simulated Microgravity-Induced Mesenchymal Stem Cell Senescence via Targeting Mitochondrial Dysfunction.

Weightlessness in space leads to bone loss, muscle atrophy, and impaired immune defense in astronauts. Mesenchymal stem cells (MSCs) play crucial roles in maintaining the homeostasis and function of the tissue. However, how microgravity affects the characteristics MSCs and the related roles in the pathophysiological changes in astronauts remain barely known. Here we used a 2D-clinostat device to simulate microgravity. Senescence-associated-ß-galactosidase (SA-ß-gal) staining and the expression of senescent markers p16, p21, and p53 were used to evaluate the senescence of MSCs. Mitochondrial membrane potential (mΔΨm), reactive oxygen species (ROS) production, and ATP production were used to evaluate mitochondrial function. Western blot and immunofluorescence staining were used to investigate the expression and localization of Yes-associated protein (YAP). We found that simulated microgravity (SMG) induced MSC senescence and mitochondrial dysfunction. Mito-TEMPO (MT), a mitochondrial antioxidant, restored mitochondrial function and reversed MSC senescence induced by SMG, suggesting that mitochondrial dysfunction mediates SMG-induced MSC senescence. Further, it was found that SMG promoted YAP expression and its nuclear translocation in MSCs. Verteporfin (VP), an inhibitor of YAP, restored SMG-induced mitochondrial dysfunction and senescence in MSCs by inhibiting YAP expression and nuclear localization. These findings suggest that YAP inhibition alleviates SMG-induced MSC senescence via targeting mitochondrial dysfunction, and YAP may be a potential therapeutic target for the treatment of weightlessness-related cell senescence and aging.

Association of the triglyceride-glucose index with coronary artery disease complexity in patients with acute coronary syndrome.

AIM: The triglyceride-glucose (TyG) index has been shown to be an independent predictor for the progression and prognosis of coronary artery disease (CAD). Whether the TyG index predicts the severity of CAD in patients presenting with acute coronary syndrome (ACS) remains unknown. METHODS: A total of 1,007 individuals presenting with ACS undergoing coronary angiography were stratified according to the tertiles of the TyG index and The Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score ≤ 22 versus SYNTAX score > 22). CAD complexity was determined by the SYNTAX score. RESULTS: After adjusting for multiple confounding factors, the TyG index was still an independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 2.6452, 95% CI 1.9020-3.6786, P < 0.0001). Compared with the lowest tertile of the TyG (T1) group, the risk for a mid/high SYNTAX score in the T2 and T3 groups was 2.574-fold higher (OR, 2.574; 95% CI 1.610-4.112; P < 0.001) and 3.732-fold higher (OR, 3.732; 95% CI 2.330-5.975; P < 0.001), respectively. Furthermore, there was a dose‒response relationship between the TyG index and the risk of complicated CAD (SYNTAX score > 22; nonlinear P = 0.200). The risk for a mid/high SYNTAX score in the T2 and T3 groups was significantly higher in normoglycemia, prediabetes mellitus, and diabetes mellitus subgroups. CONCLUSIONS: A higher TyG index was associated with the presence of a higher coronary anatomical complexity (SYNTAX score > 22) in ACS patients, irrespective of diabetes mellitus status. The TyG index might serve as a noninvasive predictor of CAD complexity in ACS patients and could potentially influence the management and therapeutic approach.