Intramyocardial Injection of Recombinant Adeno-Associated Viral Vector Coexpressing PR39/Adrenomedullin Enhances Angiogenesis and Reduces Apoptosis in a Rat Myocardial Infarction Model

Cotransfer of angiogenic and antiapoptotic genes could be the basis of new gene therapy strategies for myocardial infarction. In this study, rAAV-PR39-ADM, coexpressing antimicrobial peptide (PR39) and adrenomedullin (ADM), was designed with the mediation of recombinant adeno-associated virus. In vitro, CRL-1730 cells were divided into four groups, namely, the sham group, the AAV-null group, the NS (normal saline) group, and the PR39-ADM group. Immunocytochemistry analysis, CCK-8 assays, Matrigel assays, and apoptotic analysis were performed; in vivo, myocardial infarction model was established through ligation of the left coronary artery on rats, and treatment groups corresponded to those used in vitro. Myocardial injury, cardiac performance, and the extent of myocardial apoptosis were assessed. Results suggested that rAAV-PR39-ADM administration after myocardial infarction improved cell viability and cardiac function, attenuated apoptosis and myocardial injury, and promoted angiogenesis. Subsequently, levels of 6×His, HIF-1α, VEGF, p-Akt, Akt, ADM, Bcl-2, and Bax were measured by western blot. rAAV-PR39-ADM increased p-Akt, HIF-1α, and VEGF levels and induced higher Bcl-2 expression and lower Bax expression. In conclusion, our results demonstrate that rAAV-PR39-ADM mitigates myocardial injury by promoting angiogenesis and reducing apoptosis. This study suggests a potential novel gene therapy-based method that could be used clinically for myocardial infarction

Efficacy and safety of single-pill amlodipine/losartan versus losartan in patients with inadequately controlled hypertension after losartan treatment: a multicenter, double-blind, randomized phase III clinical trial

ObjectiveSingle-pill amlodipine besylate (AML) plus losartan (LOS) has been used to treat inadequately controlled hypertension after antihypertensive monotherapy; however, relevant data in China are limited. This study aimed to compare the efficacy and safety of single-pill AML/LOS and LOS alone in Chinese patients with inadequately controlled hypertension after LOS treatment.MethodsIn this multicenter, double-blind, randomized, controlled phase III clinical trial, patients with inadequately controlled hypertension after 4 weeks of LOS treatment were randomized to receive daily single-pill AML/LOS (5/100 mg, AML/LOS group, N = 154) or LOS (100 mg, LOS group, N = 153) tablets for 8 weeks. At weeks 4 and 8 of treatment, sitting diastolic and systolic blood pressure (sitDBP and sitSBP, respectively) and the BP target achievement rate were assessed.ResultsAt week 8, the sitDBP change from baseline was greater in the AML/LOS group than in the LOS group (−8.84 ± 6.86 vs. −2.65 ± 7.62 mmHg, P < 0.001). In addition, the AML/LOS group also showed greater sitDBP change from baseline to week 4 (−8.77 ± 6.60 vs. −2.99 ± 7.05 mmHg) and sitSBP change from baseline to week 4 (−12.54 ± 11.65 vs. −2.36 ± 10.33 mmHg) and 8 (−13.93 ± 10.90 vs. −2.38 ± 12.71 mmHg) (all P < 0.001). Moreover, the BP target achievement rates at weeks 4 (57.1% vs. 25.3%, P < 0.001) and 8 (58.4% vs. 28.1%, P < 0.001) were higher in the AML/LOS group than those in the LOS group. Both treatments were safe and tolerable.ConclusionSingle-pill AML/LOS is superior to LOS monotherapy for controlling BP and is safe and well tolerated in Chinese patients with inadequately controlled hypertension after LOS treatment

An intelligent course keeping active disturbance rejection controller based on double deep Q-network for towing system of unpowered cylindrical drilling platform

Funding Information: This work was supported by the National Natural Science Foundation of China (Grant No.61973172, 61973175, 62003175, and 62003177), the National Key Research and Development Project (Grant No. 2019YFC1510900), the key Technologies Research and Development Program of Tianjin (Grant No.19JCZDJC32800), this project also funded by China Postdoctoral Science Foundation (Grant No.2020M670633), and Academy of Finland (Grant No.315660). Funding Information: Academy of Finland, 315660; China Postdoctoral Science Foundation, 2020M670633; Key Technologies Research and Development Program of Tianjin, 19JCZDJC32800; National Key Research and Development Project, 2019YFC1510900; National Natural Science Foundation of China, 61973172; 61973175; 62003175; 62003177 Funding information Publisher Copyright: © 2021 The Authors. International Journal of Robust and Nonlinear Control published by John Wiley & Sons Ltd.Towing is a widely used mode of transportation in offshore engineering, and towing of unpowered platforms is of particular significance. However, the addition of unpowered facilities has increased the difficulty of ship maneuvering. Moreover, the marine environment is complex and changeable, and sudden winds or waves can have unpredictable effects on the towing process. Therefore, it is of great significance to overcome the influence of the harsh marine environment while navigating the towing system following a planned course to a target sea area. To tackle the time-varying disturbances, a course control method for a towing system of unpowered cylindrical drilling platform is designed based on double deep Q-network (DQN) optimized linear active disturbance rejection control (LADRC). To be specific, to tackle the difficulty of LADRC tuning, double DQN is applied to select the best parameters of the LADRC at any time according to the states of the system, without relying on the specific information of the modeland the controller. The course control performance of the towing system is evaluated in a simulation environment under various disturbances. Moreover, the Monte Carlo experiment is used to test the robustness of the controller when the ship's mass changes and the robustness of the proposed method is verified by testing with various heading angles. The results show that the LADRC with adaptive parameters optimized by double DQN performs well under external interference and inherent uncertainty, and compared with the traditional LADRC, the proposed method has better course control effects.Peer reviewe