Targeted alpha therapy (TAT) has emerged as a promising strategy for cancer treatment by selectively delivering high linear energy transfer (LET) alpha-emitters to tumor cells while minimizing off-target toxicity. However, the clinical translation of alpha-emitters, particularly radium-223 (Ra), remains challenging due to inefficient targeted delivery and uncontrolled release of recoil daughter products, leading to systemic toxicity.

Sepsis is a dysregulated host response to infection that frequently results in fatal multiple organ dysfunction. Despite advances in clinical identification and management, both its incidence and mortality have remained persistently high. Emerging evidence indicates that cell-free DNA (cfDNA), as a novel biomarker and molecular therapeutic target, holds promise for improving the clinical management of sepsis. cfDNA refers to DNA fragments present in body fluids, including naked DNA, membrane-coated DNA, nucleosomes, and neutrophil extracellular traps (NETs). cfDNA is released from host cells or pathogens into body fluids through pathways, such as NETosis, mitochondrial damage, cell necrosis, apoptosis, pyroptosis, and erythroblast enucleation. The released cfDNA triggers a strong inflammatory response by activating Toll-like receptor (TLR) 9, the absent in melanoma 2 (AIM2) inflammasome, and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. At the same time, cfDNA activates the coagulation cascade and inhibits anticoagulant and fibrinolytic systems through multiple mechanisms, resulting in microcirculatory disorders. These pathological effects are closely associated with sepsis-related organ dysfunction and poor prognosis. Elucidation of the release and pathological mechanisms of cfDNA provides a foundation for the development of targeted treatment strategies. Currently, molecular therapeutic approaches targeting cfDNA, including peptidylarginine deiminase (PAD) 4 inhibitors, pore-forming inhibitors, antioxidants, cfDNA scavengers, and deoxyribonucleases (DNases), have shown certain efficacy in treating sepsis and systemic inflammation. In terms of sepsis monitoring, compared with traditional markers, cfDNA exhibits extremely high timeliness and dynamic monitoring capability. cfDNA can simultaneously indicate the complex interplay among infection, host response, and organ damage, making it suitable for early diagnosis, prognosis assessment, treatment monitoring, organ function evaluation, and pathogen detection. Given its broad application prospects in the diagnosis and treatment of sepsis, this paper systematically elaborates on the mechanisms of cfDNA release and pathological effects in sepsis, reviews progress in cfDNA-targeted monitoring and therapeutic strategies, discusses technical challenges, and outlines potential future directions.

Peritoneal fibrosis represents a major clinical challenge for end-stage renal disease (ESRD) patients when they are undergoing peritoneal dialysis (PD). Single-cell RNA sequencing identified that peritoneal mesothelial cells undergo a senescence fate transition in long-term PD patients. Whereas the existence of mesothelial cell senescence and the underlying mechanisms should be thoroughly explored.

Disruptions in lipid metabolism cause numerous metabolic diseases, including obesity, diabetes, cardiovascular diseases, and liver disorders. Consequently, lipid metabolism serves as a potential therapeutic target, influencing the progression of various non-metabolic diseases such as kidney diseases, cancer, neurodegenerative disorders, aging, and bone-related diseases. The metabolic pathways involved in lipid metabolism are complex and highly interconnected. Although the abundance of metabolic targets presents opportunities for lipid metabolism regulation, the limited precision and safety of traditional therapeutic approaches remain significant challenges. These limitations have catalyzed the development of multifunctional nano-delivery platforms aimed at targeted intervention in lipid metabolic processes, further enhancing the flexibility of lipid metabolism regulation. This review outlines the latest advancements and representative applications of these multifunctional nano-delivery platforms. Notably, extensive research has been conducted on nanoparticles and liposomes, with these technologies being relatively mature. Furthermore, numerous novel biomaterials, including engineered adipocytes, exosome vesicles secreted by natural cells, smart-responsive nanomicelles, composite hydrogels, and engineered lipid droplets, are being increasingly explored. Finally, the review discusses the advantages of drug delivery strategies based on the targeted intervention of lipid metabolic processes, the limitations of current technologies, promising future research directions, and treatment challenges.

Immunotherapy for cardiovascular diseases (CVDs) holds great promise for precision management by modulating localized immune-inflammatory responses. The interplay between focal cardiovascular pathology and panvascular disease, necessitates highly integrated therapeutic strategies. Nano-technology-based theranostic platforms address this challenge by enabling both regulation and real-time imaging of immune cell activity within cardiovascular lesions. These functional nanotherapy systems not only halt disease progression at pathological sites but also reduce secondary cardiovascular events driven by shared inflammatory mechanisms. Additionally, nanoplatform-based dynamic visualization of immune cell responses facilitates adaptive, personalized interventions. This review introduces the role of immune cells in CVDs. It summarizes recent advances in nanomaterial-based immunomodulation strategies, including mechanisms of immune regulation, enhanced imaging, and therapeutic applications in atherosclerosis, myocardial infarction, ischemic stroke, abdominal aortic aneurysm, and myocarditis. Collectively, this integrated nanotheranostic paradigm establishes a robust foundation for the next generation of cardiovascular precision medicine.

Tenascin-C (TNC) is an extracellular matrix (ECM) protein involved in tissue damage and fibrosis. Chimeric antigen receptor (CAR) cell therapy is a novel therapeutic approach that has attracted increasing attention in recent years. Here, we engineered CAR-macrophages targeting TNC (TNC-CAR-Ms) and explored the underlying mechanism through which TNC-CAR-Ms treat liver fibrosis.

The global increase in the incidence of early-onset cancers (defined as cancers diagnosed at 20-49 years old) is a serious public health problem. We investigated 1) whether the incidence trend of early-onset cancers differs from that of later-onset cancers and 2) whether both the incidence and mortality of early-onset cancers have increased concurrently.

Ferroptosis, a form of iron-dependent regulated cell death (RCD), is emerging as a critical mechanism in the pathogenesis and progression of sepsis. This review highlights the intricate molecular pathways and hallmark features of ferroptosis, including lipid peroxidation, dysregulation of iron metabolism, and glutathione depletion, which exacerbate sepsis progression and sepsis-associated multi-organ damage. The systemic interactions of ferroptosis with inflammation, innate, and adaptive immunity, and organ injury are elucidated, emphasizing the role ferroptosis plays both in immunity including sepsis-associated immune cell damage/dysfunction, immune dysregulation, and immunosuppression, and in sepsis-associated multi-organ injury such as acute lung injury (ALI), acute kidney injury (AKI), acute hepatic injury (AHI), acute intestinal injury, septic cardiomyopathy, and septic encephalopathy. Therapeutic strategies targeting ferroptosis hold promise for improving sepsis outcomes. Approaches include pharmacological interventions of ferroptosis-associated pathways, nanoparticle-based delivery systems, and combinatorial therapies aimed at preventing immune dysfunction and protecting against multi-organ failure. Nonetheless, challenges remain in translating preclinical findings into clinical application, necessitating further research into ferroptosis-specific regulatory networks. This review underscores the potential of therapeutics targeting ferroptosis as a transformative approach to addressing sepsis, paving the way for innovative and precision-based clinical interventions.

Risk-adapted colorectal cancer (CRC) screening has the potential to balance effectiveness with resource demands, yet evidence comparing it with established methods remains limited. This study aims to compare outcomes of risk-adapted CRC screening with colonoscopy and fecal immunochemical test (FIT) strategies.

Venous thromboembolism (VTE) management in adult burn patients has become a crucial focus in China. The intricate nature of VTE necessitates specialized anticoagulation strategies due to the unique challenges posed by burn injuries. To address this pressing issue, the Burn and Trauma Branch of the Chinese Geriatric Medical Association and Critical Care Group of Burn Surgery Branch of the Chinese Medical Association organized a panel of domestic experts in burn surgery, critical care medicine, vascular surgery, nursing, and health statistics and methodology from Chinese hospitals to discuss VTE-related issues in burn injury, the heightened risk factors such as extensive tissue damage and prolonged immobilization, and the delicate balance required in anticoagulation therapy to mitigate bleeding risks. Based on the latest available research evidence as well as the clinical experience of the panel experts, this consensus comprehensively evaluates factors such as generalizability, suitability, and the potential implications for resource allocation. It also appropriately weighs the clinical advantages against possible drawbacks, resulting in the formulation of 21 guideline recommendations.Registration Practice Guideline REgistry for transPAREncy (PREPARE): No. 2023CN656.

Systemic complications are common after acute brain injury (ABI) and may trigger coagulation cascades, systemic inflammation, as well as dysfunction of the cardiovascular, respiratory, and gastrointestinal systems, etc. The pathogenesis of these systemic manifestations is multifactorial but not yet fully elucidated. This paper introduces the novel term neurogenic organ dysfunction syndrome (NODS) to characterize systemic instability arising from internal and external perturbations of the neuronal center following ABI. Elucidating the central neurogenic mechanisms of NODS is critical for early detection and prevention of complications, thereby reducing mortality and improving patient outcomes following ABI. In this paper, we explore the potential central neurogenic mechanisms of NODS from the perspective of complex brain network theory, focusing on the structural network of the central autonomic system (CAS) that maintains systemic stability, and the functional network governed by the central stress system (CSS). The CAS can be divided into the cortical autonomic network, which involves higher cortical regions, and the subcortical autonomic network, which is relatively conserved, with its main connections located in deep brain structures. The CSS is a large-scale complex network characterized by hierarchy, hubs, and modularity, which together enable the competitive optimization of functional segregation and integration. Under physiological conditions, modules (mediating functional segregation) and hubs (functional integration) within the CSS dynamically trade-off with each other to maintain the overall homeostasis. However, this balance is disrupted following pathological insults or injury, resulting in weakened functional integrity of the CSS following ABI, impaired module activity, and disturbed hub integration. This paper also demonstrates the distinct pathological manifestations arising from disturbances at different levels of the homeostatic system. Finally, this study proposes potential clinical interventions, including analgesia and sedation, neuromodulation, and receptor regulation, for early interventions and potential treatment of NODS, aiming to improve patient outcomes.

The worldwide dissemination of drug-resistant tuberculosis (TB) presents significant obstacles to conventional anti-TB treatment and prevention methods based on bactericidal antimicrobial drugs, greatly impeding advancements in combating this most lethal disease. With growing insights into the immunopathogenesis of TB, we are increasingly recognizing the potential of immunotherapeutic strategies aimed at targeting the host. After invading the host, Mycobacterium tuberculosis (M. tuberculosis) induces host cell exhaustion through its own molecules, such as early secretory antigen target-6 (ESAT-6) and di-O-acyl-trehalose, manifested as suppressed proliferative capacity, cytokine production, and cytotoxicity, thereby triggering the onset of TB. In response to this pathogenic mechanism, immunotherapeutic strategies, including cell therapy and immune checkpoint inhibitors, have been developed to promote cytokine production, activate immune cells to exhibit anti-TB activities such as autophagy, and restore immune homeostasis, including the balance between T helper 1 (Th1) and Th2 responses. These approaches have shown promise in restoring host immunity and demonstrating therapeutic effects against TB. However, a comprehensive evaluation of factors such as drug safety, optimal treatment duration, and others, is essential before these strategies can be integrated into routine clinical TB management. The advancement of immunotherapy has the potential to revolutionize current TB management and provide further benefits to patients. This review aims to comprehensively explore the advancements in diverse TB immunotherapeutic strategies, including efficacy, safety, and administration methods, and to explore the challenges and prospects of TB immunotherapy.

Clonal hematopoiesis of indeterminate potential (CHIP), driven by leukemia-related somatic mutations in hematopoietic stem cells, previously recognized as a major risk factor for hematological malignancies, has now emerged as a potent risk factor for chronic inflammation and diverse non-hematologic diseases. CHIP-associated DNA methyltransferase 3 alpha (DNMT3A), tet methylcytosine dioxygenase 2 (TET2), and additional sex combs like 1 (ASXL1) mutations alter epigenetic programs, skew myelopoiesis, and increase proinflammatory cytokines, resulting in chronic inflammation and immune imbalance. This review integrates mechanistic insights with clinical evidence to delineate CHIP's roles in solid tumors, cardiovascular disorders, and metabolic dysregulation, with an extended discussion of renal dysfunction and neurodegenerative conditions. Furthermore, we also discuss CHIP's diagnostic and therapeutic impacts across multiple disease contexts, advocating for mutation-specific diagnostic paradigms to guide therapeutic interventions.

Monkeypox, a zoonotic illness caused by monkeypox virus (MPXV), has been declared a public health emergency of international concern by the World Health Organization (WHO) on 2 separate occasions. The rapid spread and widespread transmission are closely associated with various proteins involved in the MPXV lifecycle, particularly surface antigen proteins found in mature virion (MV) and enveloped virion (EV), such as A29L, M1R, B6R, and A35R. These antigens are highly conserved in monkeypox virus (MPXV) and vaccinia virus (VACV), possessing cross-protective capabilities that can trigger broad immune protection against multiple orthopoxviruses, including MPXV. Vaccines based on DNA, mRNA, and recombinant proteins, targeting these antigens effectively address the current lack of specific monkeypox vaccines by triggering strong immune responses and ensuring the prevention of monkeypox. Compared to traditional vaccines, multi-epitope vaccines designed using computational tools such as reverse vaccinology and immunoinformatics offer lower development costs and faster validation processes. These multi-epitope vaccines also provide adaptability to mutations in MPXV strains. Additionally, these antigens and corresponding antibodies are useful for diagnosis and therapeutic monitoring, supporting early detection and offering novel treatments for cases resistant to existing antiviral drugs. This review provides a brief summary of recent progress and emerging trends in monkeypox detection, vaccine development, and antibody-based therapy targeting these antigens, offering new insights for monkeypox prevention and control.

Diabetic foot ulcers (DFU), perpetually trapped in a vicious cycle of inflammation and ischemia, remain a significant clinical challenge. Exosomes (Exo) therapy holds promise for tissue repair, yet its functional potency and delivery efficiency are often limited.

Cancer neuroscience, an emerging convergent discipline, offers novel insights into the dynamic interplay between the nervous system and cancer progression. Bidirectional signaling between the nervous system and tumors, particularly within the innervated tumor microenvironment (TME), modulates key cancer hallmarks, including proliferation, immune evasion, angiogenesis, and metastasis. Neural ablation shows heterogeneous outcomes depending on nerve subtype and tumor context, underscoring the importance of nerve-type-specific and context-dependent therapeutic approaches. These mechanistic advances are catalyzing novel therapeutic strategies that target neural-TME interactions through the integration of neuroscience and oncology. Here, we highlight recent progress in cancer neuroscience and propose revised therapeutic frameworks aimed at the neuro-innervated TME. These strategies employ interdisciplinary approaches, such as drug repurposing [β-adrenergic receptor (β-AR) blockers, antipsychotics, antidepressants], and nanotechnology-enabled targeted delivery. Both preclinical and clinical data support the potential of neural-targeted therapies to improve precision, circumvent drug resistance, and enhance clinical outcomes. By bridging neuroscience and oncology, this framework delineates a translational pathway for harnessing neural-tumor crosstalk, presenting a promising avenue for advancing cancer therapeutics and improving patient care.

Traumatic amputations have increased worldwide over the past two decades and are expected to increase by 72% by 2050. Surgical replantation provides superior functional recovery and patient satisfaction but is limited to specialized centers and restricted by short ischemia times, due to life-over-limb prioritization in patient care. To overcome these limitations, we developed an ex vivo limb perfusion system (EVEP) to extend limb viability and, for the first time, investigate its impact on peripheral nerve regeneration, a key prerequisite for functional recovery following replantation.