Alzheimer’s disease (AD) is a severe neurodegenerative disorder with a growing global burden. With the rising incidence of AD, the need for novel therapeutic targets has become increasingly critical. TREM2, a receptor expressed on microglial cells, plays a crucial role in modulating neuroinflammation and clearing pathological substrates, making it a promising candidate for AD therapy. However, the recent clinical trial INVOKE-2 failed to demonstrate significant clinical benefits of the TREM2-targeted antibody AL002, raising doubts about the efficacy of TREM2-targeted methods. This article examines the role of TREM2 in AD pathogenesis, evaluates potential reasons for the disappointing outcomes of the INVOKE-2 trial, and discusses future directions for TREM2-based therapies. Factors such as treatment timing, dosage optimization, patient genetic variability, and combination therapy strategies are identified as critical determinants of therapeutic success. Future studies should aim to refine treatment strategies, identify precise indications, and explore the potential for combination therapies to enhance efficacy.

Diagnosis-related groups (DRG) based hospital payment systems are gradually becoming the main mechanism for reimbursement of acute inpatient care. We reviewed the existing literature to ascertain the global use of DRG-based hospital payment systems, compared the similarities and differences of original DRG versions in ten countries, and used ischemic stroke as an example to ascertain the design and implementation strategies for various DRG systems. The current challenges with and direction for the development of DRG-based hospital payment systems are also analyzed. We found that the DRG systems vary greatly in countries in terms of their purpose, grouping, coding, and payment mechanisms although based on the same classification concept and that they have tended to develop differently in countries with different income classifications. In high-income countries, DRG-based hospital payment systems have gradually begun to weaken as a mainstream payment method, while in middle-income countries DRG-based hospital payment systems have attracted increasing attention and increased use. The example of ischemic stroke provides suggestions for mutual promotion of DRG-based hospital payment systems and disease management. How to determine the level of DRG payment incentives and improve system flexibility, balance payment goals and disease management goals, and integrate development with other payment methods are areas for future research on DRG-based hospital payment systems.

Studies have found that intermittent fasting (IF) can prevent diabetes, cancer, heart disease, and neuropathy, while in humans it has helped to alleviate metabolic syndrome, asthma, rheumatoid arthritis, Alzheimer's disease, and many other disorders. IF involves a series of coordinated metabolic and hormonal changes to maintain the organism's metabolic balance and cellular homeostasis. More importantly, IF can activate hepatic autophagy, which is important for maintaining cellular homeostasis and energy balance, quality control, cell and tissue remodeling, and defense against extracellular damage and pathogens. IF affects hepatic autophagy through multiple interacting pathways and molecular mechanisms, including adenosine monophosphate (AMP)-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), silent mating-type information regulatory 2 homolog-1 (SIRT1), peroxisomal proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR), as well as signaling pathways and molecular mechanisms such as glucagon and fibroblast growth factor 21 (FGF21). These pathways can stimulate the pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), play a cytoprotective role, downregulate the expression of aging-related molecules, and prevent the development of steatosis-associated liver tumors. By influencing the metabolism of energy and oxygen radicals as well as cellular stress response systems, IF protects hepatocytes from genetic and environmental factors. By activating hepatic autophagy, IF has a potential role in treating a variety of liver diseases, including non-alcoholic fatty liver disease, drug-induced liver injury, viral hepatitis, hepatic fibrosis, and hepatocellular carcinoma. A better understanding of the effects of IF on liver autophagy may lead to new approaches for the prevention and treatment of liver disease.

The COVID-19 global pandemic of the past two years has changed the way humans behave, the way governments respond to crises, and placed a heavy burden on the health care systems of the countries in question. As 2022 begins, the world is experiencing a huge wave of infection with the Omicron variant of SARS-CoV-2 due […]

Respiratory disease deaths associated with seasonal influenza are estimated to be 290,000 to 650,000 per year globally. In Japan, seasonal influenza affects more than 10 million people per year, and especially children, the elderly, and patients with underlying medical conditions, and seasonal influenza can cause severe illness. As SARS-CoV-2 continues to spread, the combined risk of concurrent influenza epidemics and the COVID-19 pandemic are a concern. When the status of influenza virus infections during the 2020-2021 flu season was compared to the 2011 to 2020 flu seasons, data indicated the absence of seasonal influenza outbreaks in Japan during the COVID-19 pandemic. The number of flu patients was roughly estimated to be 14,000 nationwide from September 2020 to March 2021, which marks the first sharp decrease since national influenza surveillance started in 1987 in conjunction with National Epidemiological Surveillance of Infectious Diseases (NESID). Moreover, approximately 500 sentinel sites (designated medical facilities) nationwide reported only 112 patients with severe influenza who required hospitalization. Since prevention and control measures amidst the COVID-19 pandemic have become the "new normal", one can reasonably assume that the absence of a seasonal influenza outbreak is related to prevention and control measures implemented in response to the COVID-19 pandemic. Basic infection prevention measures were thoroughly implemented, such as wearing masks, handwashing, and avoiding confined spaces, crowded places, and close-contact settings. More importantly, the behavioral changes adopted to constrain COVID-19 during three declared states of emergency reduced population density and contact with people, including closing schools, asking restaurants to reduce their business hours, teleworking, curbing the flow of people during vacation week, etc. These behavioral changes will serve as a valuable reference to reduce the spread of seasonal influenza in the future.

Diet and circadian rhythms have been found to have a profound impact on health, disease, and aging. Skipping breakfast, eating late, and overeating have adverse effects on the body's metabolism and increase the risk of cardiovascular and metabolic diseases. Disturbance of circadian rhythms has been associated with increased risk of atherosclerosis, Alzheimer's disease, Parkinson's disease, and other diseases. Abnormal deposition of amyloid β (Aβ) and tau proteins in the brain and impaired synaptic function are linked to cognitive dysfunction. A restrictive diet following the circadian rhythm can affect the metabolism of lipids, glucose, and amino acids such as branched chain amino acids and cysteine. These metabolic changes contribute to autophagy through molecular mechanisms such as adenosine monophosphate-activated protein kinase (AMPK), rapamycin (mTOR), D-β-hydroxybutyrate (D-BHB), and neuropeptide Y (NPY). Autophagy, in turn, promotes the removal of abnormally deposited proteins and damaged organelles and improves cognitive function, ultimately prolonging lifespan. In addition, a diet restricted to the circadian rhythm induces increased expression of brain-derived neurotrophic factor (BDNF) in the forebrain region, regulating autophagy and increasing synaptic plasticity, thus enhancing cognitive function. Consequently, circadian rhythm-restricted diets could serve as a promising non-pharmacological treatment for preventing and improving cognitive dysfunction and prolonging lifespan.