Military Medical Research最新文献

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.

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.

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.

Background: 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.

Methods: Hind limbs of 6 healthy pigs were amputated, and after 2 h of warm ischemia, limbs were either perfused normothermally for 6 h with PerfadexPlus® ± medication using in-house developed EVEP or stored statically (4 °C vs. room temperature). Perfusion parameters, blood gas analysis, serum markers, cytokine levels, thermal imaging, colloid oncotic pressure, weight gain, joint mobility, peripheral nerve histomorphometric and stereological analyses were performed.

Results: Data confirm a valid and reliable EVEP with an optimized perfusion protocol. Comparison of perfusion groups revealed lower serum injury markers in the medication group, which included methylprednisolone treatment. Additionally, the medication group exhibited reduced weight gain and preserved unrestricted joint mobility, but concurrently led to a significant decrease in pro-regenerative cytokine levels associated with Wallerian degeneration (WD).

Conclusions: In general, EVEP mitigates ischemia-related damage and facilitates ex vivo induction of WD, a critical prerequisite for nerve regeneration, functional recovery, and prevention of neuroma formation with subsequent phantom pain, by establishing the pro-regenerative environment for WD, which is further amplified by omitting the anti-inflammatory methylprednisolone.

Background: 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.

Methods: We proposed an integrated strategy combining trace elements (TE) programming, Exo engineering, and intelligent delivery to overcome both functional and delivery constraints. Multiple TE (Fe, Mg, Zn, Mn, and Se) were incorporated into a three-dimensional (3D) dynamic culture system to construct high-activity engineered Exo (3D-TE-Exo). The biological mechanisms were explored via transcriptomics, mitochondrial function assays, and oxidative stress analyses. A dual-network hydrogel, incorporating dynamic Schiff base bonds and ultraviolet (UV)-triggered disulfide bond reorganization, was developed for precise and sustained Exo release in vivo.

Results: 3D-TE-Exo achieved a yield of 1.9 × 10¹² particles/ml, representing a 29-fold increase over conventional culture (6.5 × 10¹⁰ particles/ml). These Exo modulated the complement pathway, restored mitochondrial membrane potential, enhanced adenosine triphosphate (ATP) production, and activated autophagy, thereby alleviating oxidative stress, with complement 1q binding protein (C1QBP) identified as a key mediator. The hydrogel enabled prolonged Exo retention and controlled release at the wound site. In DFU rat models, this system achieved 89.71% wound closure by day 14, significantly higher than the 50.64% observed in controls.

Conclusions: This study presents a synergistic approach integrating engineered Exo and smart biomaterials to accelerate DFU healing. The platform offers a multi-target intervention strategy with strong translational potential for the clinical management of chronic wounds.

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.

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.

Background: Lung invasive mucinous adenocarcinoma (LIMA) is a rare, unique, and heterogeneous subtype of lung cancer whose patterns of lymph node (LN) metastasis are unknown, and a consensus on LN dissection (LND) has not been reached. This study aimed to evaluate LN metastasis patterns in LIMAs and establish optimal LND strategies.

Methods: Data about 19,596 LNs from 1474 LIMA patients collected between January 2010 and December 2021 at 8 lung cancer research centers and tertiary hospitals across China, and data from 5304 LIMA patients between 2004 and 2021 in the SEER database were analysed. Metastasis probabilities were calculated for each LN station to construct a metastasis atlas. Statistical methods, including LOWESS fitting, restricted cubic spline, Kaplan-Meier, and logistic regression analyses, were employed to identify optimal LND strategies.

Results: Compared with non-mucinous adenocarcinoma patients, LIMA patients exhibited distinct clinicopathological features and a significantly lower probability of LN metastasis (4.20% vs. 7.19%, P < 0.05). Metastasis was most common in the peripheral and hilar/interlobar zones (especially stations 14 and 10), with minimal involvement in the lower zone (stations 8 and 9). A U-shaped relationship between the LN count and prognosis (including overall survival, relapse-free survival, and cancer-specific survival) was found, with 6-20 and 18 LNs as the optimal range and cut-off point, respectively. Excessive or insufficient dissection was linked to poorer outcomes. A predictive model (area under the receiver operating characteristic cure = 0.8367) revealed that patients with a probability ≥ 0.5 had a significantly greater proportion of patients with stage N1+ disease (including N1 and N2 patients) (68.09% vs. 11.63%, P < 0.001) and worse overall survival [hazard ratio (HR) = 4.00, 95% CI 2.72-5.87, P < 0.001] and relapse-free survival (HR = 5.53, 95% CI 3.97-7.71, P < 0.001). The minimum numbers of LNs for the low- (probability < 0.1), medium- (probability 0.1-0.5), and high- (probability > 0.5) risk patients were 7, 14, and 17, respectively. For those with uncertain metastatic risk, dissecting 18 LNs may be the most appropriate and robust strategy.

Conclusions: This study systematically revealed the pattern of LIMA-specific LN metastasis and proposed a risk-stratified LND strategy. These recommendations balance the imperatives of accurate staging with the preservation of long-term patient prognosis, offering a practical guideline for surgical decision-making.