Medical review (Berlin, Germany)最新文献

Liver metastases pose a serious challenge in the field of systemic cancer treatment, as this organ has a particular microenvironment that favours malignant cells disseminating to settle there. We outline major steps of liver immune tolerance in metastasis including pre-metastatic niche formation, immune evasion during circulation, establishment of an intrahepatic immune desert and metabolism, myeloid cell networks and gut microbiome-mediated coordinated tolerance. We then combine new combination and integrative therapies that are intended to break this tolerance; these include immunochemotherapy regimens, synergistic antiangiogenics and immunotherapies, dual immune checkpoint blockade and myeloid-cell reprogramming, combined locoregional and systemic therapies and new microenvironmental targeting. Each strategy is assessed with regard to its potential disruption of hepatic immune quiescence, improved clinical translation and durable antitumour activity. We suggest a proposed solution termed Liver-metastasis-oriented shared-mechanism therapeutic strategy, which may target multiple metastatic bottlenecks due to similarities. This framework provides a basis for personalizing combination therapies and designing future clinical trials for treating liver metastases, with organ-specific considerations and will be the subject of a commentary.

Bioactive lipids are low-abundance, rapidly acting signaling molecules that orchestrate vascular homeostasis and remodeling through a closed-loop cycle of synthesis, localization, receptor/effector sensing, and inactivation. This review delineates the major bioactive lipid classes - eicosanoids, lysophospholipids, sphingolipids, and sterol-derived mediators - linking their enzymatic pathways, transport mechanisms, receptor networks, and termination routes to vascular physiology and disease. Centered on vascular homeostasis and remodeling, we summarize the roles of bioactive lipids across atherosclerosis, aneurysms, hypertension, and thrombosis. Collectively, these findings underscore the pivotal role of bioactive lipid signaling in cardiovascular disease, suggesting that these pathways and receptors may serve as promising targets for diagnosis and therapy.

China's healthcare system has made significant progress in the past 20 years, but disparities between urban and rural areas persist. The New England Journal of Medicine (NEJM) launched a pilot initiative to address these gaps through four core approaches: translation and dissemination of medical evidence, digital continuing medical education (CME), building research capacity, and fostering global health collaboration. Over the past decade, NEJM's Chinese-language platform has translated 1,709 high-impact articles, making them accessible to clinicians nationwide. Digital CME initiatives, accelerated by the COVID-19 pandemic, have enabled real-time knowledge sharing, reaching 450,000 physicians. Collaborative training programs have equipped clinicians with essential research skills. These efforts have shown measurable impact, with a sharp increase in original research submissions and publications from China-based authors since 2014. While progress has been made, further focus on knowledge dissemination, equitable access to CME, research capacity building, and global engagement is crucial for advancing China's healthcare system.

The integration of Artificial Intelligence (AI) into healthcare signifies one of the most formidable and multifaceted advancements in contemporary medicine. The relentless pace of innovation necessitates a timely synthesis of the field's trajectory, critically evaluating both the promises and complexities of this ongoing transformation. This report aims to map the expansive terrain of AI's deployment across critical healthcare sectors, encompassing clinical decision support, diagnostic imaging, pharmaceutical innovation, biomedical research, and regulatory review. It begins with an analysis of the opportunities and challenges inherent in the real-world implementation of AI technologies, systematically categorizing their adoption and utilities into three core domains: (1) clinical informatics and healthcare delivery, (2) clinical sciences and therapeutic interventions, and (3) drug development and biomedical investigation. Thereafter, the discussion turns to AI's role within the regulatory landscape for drug and medical product reviews and approvals. Adopting a progressive outlook, the author formulates strategic recommendations aimed at surmounting potential barriers, thus facilitating the judicious, efficacious, and equitable integration of AI. Collectively, these analyses provide a narrative that highlights both the transformative potential and the pragmatic imperatives of deploying AI to improve human health.

Transfer RNA-derived small RNAs (tsRNAs), a class of non-coding RNAs derived from precursor or mature tRNAs, are now recognized as critical regulators in response to cellular stress. tsRNAs exhibit differential expression during brain aging and in age-related neurodegenerative disorders such as Alzheimer's disease (AD), suggesting their involvement in the molecular processes underlying neuronal aging and degeneration. This article summarizes recent advances in our understanding of tsRNA biogenesis, classification, and function, emphasizing their regulatory role in brain aging and AD pathology. We also highlight the diagnostic and therapeutic implications of tsRNAs and discuss future directions for exploring their mechanistic and clinical relevance.

T cell-mediated immune response is the center of adaptive immunity. Despite more than five decades of research, the knowledge of mechanisms drives the initiation of T cell-mediated immune response is still limited due to the complexity of T cell-mediated immunity. Based on the accumulating evidences of Th1-mediated immune response, a "priming-activation" model was proposed to describe the initiation of the immune response. In this model, naïve CD4 T cells undergo a priming phase in the draining lymph nodes (dLNs) to polarize to Th1 fate by signals from dendritic cells (DCs). The primed Th1 cells then migrate to the antigen-affected loci and encounter antigen presenting cells (APCs) again. With signals from these cells, the primed Th1 cells differentiate to activated effector cells to coordinate Th1-centered immunity, which is the activation phase of Th1-mediated immune response. Recently, a model for the initiation of Th2-mediated immunity has been proposed, which highly resembles the priming-activation model for Th1 cells. We summarize the advances of Th17-mediated immunity and our understanding of it, and propose a two-step model for the initiation of Th17-mediated autoimmune immunity. Our model is similar to the priming-activation model of Th1 cells, as well. Although there are major knowledge gaps on molecular and cellular mechanisms in our model to be addressed, we hope that this model, with the associated gaps being addressed, will provide framework for research on the initiation of Th17-mediated immune responses and eventually enhances our understanding of how T cell-mediated immunity initiates.

In recent years, the global prevalence of overweight and obesity has exhibited a sustained upward trajectory. As an independent entity within the spectrum of chronic diseases, obesity serves as a significant pathogenic factor for multiple chronic conditions and ranks as the sixth leading risk factor for mortality and disability nationwide. It poses a severe threat to public health while imposing a considerable socioeconomic burden. The etiology of obesity is multifactorial; however, primary diagnostic modalities and therapeutic approaches remain relatively undiversified, and long-term weight maintenance remains challenging. Similar to other chronic diseases, obesity management demands a long-term multimodal strategy. This strategy must incorporate individualized treatment goals and balance the benefits and risks of different interventions to formulate personalized management plans. These plans aim to reduce body weight through multifaceted interventions, alleviate obesity-related comorbidities, enhance quality of life, and optimize overall health outcomes.

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.

RNA-based medicines have transformed modern therapeutics, exemplified by the clinical success of small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and mRNA vaccines. Small self-cleaving ribozymes - compact catalytic RNA species capable of programmable cleavage and ligation - were among the earliest RNA drugs explored, yet their progress was initially hindered by instability, nuclease degradation, inefficient intracellular delivery, and immune activation. In this Perspective, we discuss how recent technological convergence has revived their potential. Comparative genomics has uncovered new catalytic classes, including Twister, Pistol, Hatchet, and Hovlinc ribozymes, thereby expanding the catalytic repertoire. High-resolution structural and computational studies have elucidated their reaction architectures, while chemical modifications and advanced nanocarrier systems - such as DNA nanostructures, spherical nucleic acids, and lipid nanoparticles - have markedly improved molecular stability and delivery efficiency. Emerging applications, from ligand-responsive aptazymes and ribozyme-SNA conjugates to the StitchR RNA trans-ligation platform, further illustrate the expanding biomedical versatility of catalytic RNA. Together, these advances are redefining the role of ribozymes in oncology, virology, and genetic medicine. No longer a dormant concept, ribozymes now stand as an evolving frontier - rationally engineered catalysts that continue to inspire technological creativity and renewed optimism in RNA therapeutics.

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.