Medical review (Berlin, Germany)最新文献

Gastrointestinal (GI) complications are prevalent and severe clinical challenges encountered in critically ill patients. They are closely linked to disease progression, increased morbidity and mortality, and escalating healthcare expenses. This comprehensive review summarizes the epidemiology of GI complications in critically ill patients, elucidating the underlying pathophysiological mechanisms including hemodynamic alterations, inflammatory cascades, neuro-endocrine dysregulation, and gut microbiota imbalance. It confers distinctive clinical manifestations and effective diagnostic approaches. Therapeutic strategies, encompassing nutritional support, pharmacological management, and surgical or interventional procedures will be discussed. The review also briefly introduces the concept of the "gut-organ axis," emphasizing how intestinal barrier disruption and dysbiosis can disseminate inflammatory and metabolic signals to distant organs such as the lungs, liver, kidneys, and brain, thereby underscoring the need for clinicians to recognize systemic effects. In essence, prompt identification and multimodal intervention are pivotal for optimizing outcomes in critically ill patients; judiciously addressing GI complications in clinical decision-making can mitigate morbidity and enhance both short-term and long-term prognosis.

Aging and metabolic diseases are intricately linked through bidirectional molecular mechanisms that foster a harmful cycle of physiological decline. This cycle is driven by several key factors, including altered nutrient sensing, mitochondrial dysfunction, cellular senescence, chronic inflammation, epigenetic modifications, circadian rhythm disruptions, and imbalances in the gut microbiota. Emerging interventions targeting this aging-metabolism axis hold significant promise for extending healthspan. These approaches include the use of pharmacological mimetics, senolytics, multi-omics strategies, and microbiome modulation, all of which aim to restore metabolic homeostasis and mitigate age-related pathologies. However, several challenges remain in translating these strategies into clinical practice. These include the need for tissue-specific targeting, ensuring the long-term safety of interventions, and addressing socioeconomic disparities in healthcare access. Future research efforts are focusing on integrating multi-omic technologies, organoid and human cellular models, and developing equitable precision medicine frameworks. These initiatives aim to extend healthspan and reduce the global impact of aging-related metabolic diseases.

G protein-coupled receptors (GPCRs) actively participate in crucial cellular processes such as cell proliferation, differentiation, and communication. GPCRs play a pivotal role in the initiation and progression of tumors. In this review, focusing on non-small-cell lung cancer (NSCLC), one of the most prevalent cancers, we highlight the roles of GPCRs including understudied receptors in cancer oncogenesis and progression. We summarize current knowledge on GPCR functions in NSCLC, detailing their contributions to tumor development, progression, and therapy resistance. Furthermore, we evaluate the therapeutic potential of agents targeting GPCR-driven tumorigenic signaling in lung cancer. Critical knowledge gaps in understanding GPCR involvement in NSCLC biology are identified, and we address the limitations and challenges of targeting GPCRs for NSCLC treatment. This review provides insights into the current landscape, recent progress, and persisting challenges in developing GPCR-targeted anticancer therapies.

N-methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) mediate the majority of excitatory synaptic transmission in central nervous system. Dysfunction of these receptors may result in various diseases, including epilepsy. In recent years, a growing number of studies have targeted NMDARs and AMPARs to screen for antiepileptic agents that are both efficacious and well-tolerated. This review summarizes compounds, herbal extracts, and herbal complexes of traditional Chinese medicine (TCM) that have demonstrated antiepileptic effects through their modulation of NMDARs and AMPARs over the past 25 years. Furthermore, this review also systematically synthesizes the molecular mechanisms underlying these drugs, with the aim of facilitating the rational design and translational development of future antiepileptic therapeutic agents.

Modern biomedical sensing increasingly demands technologies capable of capturing structural, functional, and molecular information simultaneously. Photoacoustic (PA) and electrochemical (EC) sensing individually address these needs but exhibit inherent limitations when used alone. PA imaging offers deep-tissue, label-free visualization with high spatiotemporal resolution, yet lacks molecular specificity. Conversely, EC sensing provides quantitative, chemically specific information through electrode functionalization, but struggles with spatial mapping and noninvasive detection. Integrating these complementary modalities establishes a unified framework-Photoacoustic-Electrochemical Synergy (PAECS)-that fuses PA's noninvasive, flow-resolved optical contrast with EC's molecular selectivity and quantitative accuracy. PAECS enables multimodal sensing across scales, improving rare-event detection, dynamic monitoring of metabolic and hemodynamic processes, and mechanistic studies of disease and drug response. Applications include coupling PA flow cytometry with EC microfluidics for circulating tumor cell and biomarker analysis, as well as integrating PA imaging with EC metabolite monitoring for real-time tissue profiling. To realize PAECS, future efforts must address system co-registration, signal decoupling, and biomarker-driven design. By bridging optical, acoustic, and electrochemical information, PAECS represents a transformative step toward comprehensive, multiscale biomedical diagnostics and personalized health monitoring.

Artificial Intelligence (AI) is bringing an unprecedented evolution in human history. As it develops, the utilization of AI in clinical practice becomes one of the hot topics that attracts the attention of the medical field as well as the public. While we know that AI will be heavily involved in the medical system, a critical question is what we expect for the future AI medical doctor. To answer this question, it is important to understand that the developing patterns of any other discovery and industrialization do not fit the pattern of AI development, because it acts more like a human instead of simply being a machine or tool. Thus, AI doctors function like human doctors to provide patient-centered reasoning, intellectual judgment, and ethical decision-making rather than just mechanical data processing. Here we present such a likely development process, including current AI status, expected AI doctors, challenges, and future directions.

Once maternal-fetal immune tolerance is broken, pregnancy complications such as preeclampsia (PE) will occur. Regulatory T cells (Tregs) as unique immunosuppressive cells, play an important role in this whole process. Programmed cell death 1 ligand 1 (PD-L1) is widely expressed in human placental trophoblasts, through binding with programmed cell death protein 1 (PD-1) to maternal-fetal immunomodulation. Exosomes belong to extracellular membrane-bound microvesicles (EMV) that get more and more attention in signaling pathways and disease regulation. The role of Tregs in the development of PE and the role of PD-1/PD-L1 in regulating the function of Tregs have been studied, but the mechanism of trophoblast-derived exosomes containing PD-L1 influences PE by mediating maternal-fetal interface immunity is still unclear. In this article, our specific hypothesis is that trophoblast-derived exosomes containing PD-L1 which may decrease in PE could regulate the proportion and differentiation of Tregs in the decidua. This mechanism of suppression must be further investigated as it may provide valuable clues to novel therapeutic design in the realm of PE research.

Gastric cancer (GC), a leading global malignancy, poses a significant threat to human health. Despite substantial therapeutic advances, drug resistance remains a major challenge for many patients. Aberrant lipid metabolism represents a hallmark in tumors; it critically contributes to GC pathogenesis. This review explores key enzymes and pathways driving lipid metabolic reprogramming within the GC immune microenvironment, which facilitates tumor immune evasion and chemotherapy resistance. This review also addresses the challenges posed by lipid metabolism reprogramming in clinical treatment, explores therapeutic perspectives and novel directions, and discusses metabolism-related mechanisms.

Extrachromosomal DNA (ecDNA) drives the evolution of cancer cells. Its widespread presence in tumors and strong association with poor clinical outcomes make ecDNA a promising and broadly applicable therapeutic target. Recent studies have begun to unravel the mechanisms by which ecDNA promotes tumorigenesis and maintains its presence in cancer cells. These discoveries have paved the way for developing ecDNA-targeted therapies. In this Perspective, we summarize the latest advances in our understanding of the mechanism underlying both the ecDNA-induced cancer phenotype and ecDNA maintenance. We also explore potential strategies for targeting ecDNA in cancer treatment.

N-lactoyl-phenylalanine (Lac-Phe), an exercise-induced metabolite that suppresses appetite, has quickly emerged as a key molecule in metabolic signaling networks. Lac-Phe, following its CNDP2-mediated synthesis, mediates key appetite- and weight-modulating effects of metformin, which acts primarily by mitochondrial inhibition in gut epithelial cells. Both Lac-Phe and related N-lactoyl-amino acids serve as potent biomarkers of mitochondrial dysfunction. Elevated levels of these metabolites are found in genetic mitochondrial diseases, offering potentially superior prognostic value compared to lactate in conditions alike. Despite uncertainties regarding its specific receptor(s) and signaling mechanisms, the expanding roles of Lac-Phe underscore its critical position at the intersection of exercise physiology, pharmacology, energy metabolism, and disease pathology, suggesting significant potential for future diagnostics and therapeutics in mitochondrial and metabolic disorders.