Leiming Luo

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), infects humans through a strong interaction between the viral spike protein (S-protein) and angiotensin converting enzyme 2 (ACE2) receptors on the cell surface. The infection of host lung cells by SARS-CoV-2 leads to clinical symptoms in patients. However, ACE2 expression is not restricted to the lungs; altered receptors have been found in the nasal and oral mucosa, vessel, brain, pancreas, gastrointestinal tract, kidney, and heart. The future of COVID-19 is uncertain, however, new viral variants are likely to emerge. The SARS-CoV-2 Omicron variant has a total of 50 gene mutations compared with the original virus; 15 of which occur in the receptor binding domain (RBD). The RBD of the viral S-protein binds to the human ACE2 receptor for viral entry. Mutations of the ACE2–RBD interface enhance tight binding by increasing hydrogen bond interactions and expanding the accessible surface area. Extracorporeal membrane oxygenation, hyperbaric oxygen, and aggressive dialysis for the treatment of COVID-19 have shown various degrees of clinical success. The use of decoy receptors based on the ACE2 receptor as a broadly potent neutralizer of SARS-CoV-2 variants has potential as a therapeutic mechanism. Drugs such as 3E8 could block binding of the S1-subunit to ACE2 and restrict the infection of ACE2-expressing cells by a variety of coronaviruses. Here, we discuss the development of ACE2-targeted strategies for the treatment and prevention of COVID-19.

The nonreceptor tyrosine kinase c-Abl is inactive under normal conditions. Upon activation, c-Abl regulates signaling pathways related to cytoskeletal reorganization. It plays a vital role in modulating cell protrusion, cell migration, morphogenesis, adhesion, endocytosis and phagocytosis. A large number of studies have also found that abnormally activated c-Abl plays an important role in a variety of pathologies, including various inflammatory diseases and neurodegenerative diseases. c-Abl also plays a crucial role in neurodevelopment and neurodegenerative diseases, mainly through mechanisms such as neuroinflammation, oxidative stress (OS), and Tau protein phosphorylation. Inhibiting expression or activity of this kinase has certain neuroprotective and anti-inflammatory effects and can also improve cognition and behavior. Blockers of this kinase may have good preventive and treatment effects on neurodegenerative diseases. Cognitive dysfunction after anesthesia is also closely related to the abovementioned mechanisms. We infer that alterations in the expression and activity of c-Abl may underlie postoperative cognitive dysfunction (POCD). This article summarizes the current understanding and research progress on the mechanisms by which c-Abl may be related to postoperative neurodegeneration.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease. Most infected patients manifest mild flu-like symptoms, but in some cases, the patients rapidly develop severe lung infections and pneumonia. It is estimated that about 15–20% of patients with COVID-19 develop hypoxemia and require some form of oxygen therapy and ventilation support. Further, exacerbation of the disease usually requires an emergency tracheal intubation, where the patients are more prone to coughing and aerosol diffusion, placing the anesthesiologist at an extremely high risk of infection. In this review, after a brief introduction to the epidemiology and pathogenesis of the COVID-19, we describe various recommendations that the anesthesiologists should employ to avoid the chances of infection during the management of severely ill patients. We describe key steps such as not removing the patient's mask prematurely and using sedatives, analgesics, and muscle relaxants for rapid and orderly intubation. The use of spinal cord and regional nerve block anesthesia should also be promoted to avoid general anesthesia. Since the patients with COVID-19 may also have disorders related to other parts of the body (other than lungs), short-acting drugs are recommended to actively maintain the perfusion pressure of the peripheral and important organs without metabolism of the drugs by the liver and kidney. Multimodal analgesia is advocated, and non-steroidal anti-inflammatory analgesic drugs can be used appropriately. In this review, we also discuss key studies and experiences of anesthesiologists from China, highlights research findings, and inform on the proper management of patients with perspective on anesthesiologists.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause of hospitalizations and mortality when diagnosed at the age of ≥ 65 years. HFpEF represents multifactorial and multisystemic syndrome and has different pathophysiology and phenotypes. Its diagnosis is difficult to be established based on left ventricular ejection fraction and may benefit from individually tailored approaches, underlying age-related changes and frequent comorbidities. Compared with the rapid development in the treatment of heart failure with reduced ejection fraction, HFpEF presents a great challenge and needs to be addressed considering the failure of HF drugs to improve its outcomes. Further extensive studies on the relationships between HFpEF, aging, and comorbidities in carefully phenotyped HFpEF subgroups may help understand the biology, diagnosis, and treatment of HFpEF. The current review summarized the diagnostic and therapeutic development of HFpEF based on the complex relationships between aging, comorbidities, and HFpEF.

Due to the continued high incidence and mortality rate worldwide, there is still a need to develop new strategies for the prevention, diagnosis and treatment of cardiovascular diseases (CVDs). Proper cardiovascular function depends on the coordinated interplay and communication between cardiomyocytes and noncardiomyocytes. Extracellular vesicles (EVs) are enclosed in a lipid bilayer and represent a significant mechanism for intracellular communication. By containing and transporting various bioactive molecules, such as micro-ribonucleic acids (miRs) and proteins, to target cells, EVs impart favourable, neutral or detrimental effects on recipient cells, such as modulating gene expression, influencing cell phenotype, affecting molecular pathways and mediating biological behaviours. EVs can be released by cardiovascular system-related cells, such as cardiomyocytes, endotheliocytes, fibroblasts, platelets, smooth muscle cells, leucocytes, monocytes and macrophages. EVs containing miRs and proteins regulate a multitude of diverse functions in target cells, maintaining cardiovascular balance and health or inducing pathological changes in CVDs. On the one hand, miRs and proteins transferred by EVs play biological roles in maintaining normal cardiac structure and function under physiological conditions. On the other hand, EVs change the composition of their miR and protein cargoes under pathological conditions, which gives rise to the development of CVDs. Therefore, EVs hold tremendous potential to prevent, diagnose and treat CVDs. The current article reviews the specific functions of EVs in different CVDs.