Biofilm-associated infections present a critical therapeutic challenge due to antibiotic resistance and impaired tissue healing. Here, we present a microrobotic system (MZ-8) that integrates real-time human-steered navigation with autonomous, microenvironment-responsive therapy to actively eradicate biofilms and promote tissue regeneration. This microrobotic system features a spine-inspired structure for mechanical biofilm disruption, a pH-responsive ZIF-8 coating for immunomodulatory Zn2+ release, and closed-loop actuation under second near-infrared fluorescence guidance. In a rat model of periprosthetic joint infection, MZ-8 achieved effective biofilm removal, induced a pro-regenerative immune response by polarizing macrophages toward the M2 phenotype, and significantly enhanced tissue regeneration. Transcriptomic analysis further revealed the activation of immunomodulatory pathways and upregulation of M2-associated genes, confirming the system's sequential shift from eradication to repair. Moreover, validation in a rabbit model and human knee joint confirmed its operational feasibility under clinical imaging guidance and excellent biosafety. This work establishes that integrating physical eradication, biochemical immunomodulation, and interactive control within a single system is essential for advancing from infection clearance to functional tissue restoration. Thus, it provides a therapeutic paradigm for biofilm-associated diseases and lays a foundation for future intelligent, clinically adaptive anti-infective systems.

Cell migration serves as a crucial factor in cell therapy, which has been extensively studied in vitro. However, the impact of in vivo migratory behavior of cells on therapeutic efficacy remains an uncharted territory, due to the complexity of biological processes within living organisms. Here, tendon stem/progenitor cells (TSPCs) with or without mechanical confinement simulating sedentary and migratory cell behaviors were sophisticatedly designed and transplanted to patellar tendon defect mouse model, with short-wave infrared (SWIR) fluorescence imaging adopted to dynamically monitor in vivo cell migration process. As a result, migratory TSPCs exhibited enhanced morphological plasticity with substantial changes in area (51.47% vs. 17.06%, p < 0.05) and width (41.11% vs. 8.69%, p < 0.05) of cell population. Besides, directional in vivo cell migration pattern from injection site to the proximal and medial region of patellar tendon defect was depicted, which further led to superior therapeutic efficacy in tendon regeneration based on histological scoring. In contrast, sedentary TSPCs demonstrated prolonged in vivo cell retention in large cell numbers (21 d vs. 14 d), and resulted in inferior therapeutic efficacy. Furthermore, transcriptomic analysis revealed activations of cell chemotaxis and migration pathways in mice with migratory TSPCs, while morbid pathways of excessive cell proliferation and ossification in sedentary TSPCs. In summary, in vivo cell migratory behavior was identified as a major driver of superior therapeutic efficacy in tendon regeneration by morphological plasticity and directional migration. This study highlights the pivotal role of in vivo migration competence in cell therapy optimization and provides a mechanistic framework for clinical translation strategies.

Adipose-derived stem cells extracellular vesicles (ADSCs-EVs) hold significant promise in tissue repair and regeneration. While they have been reported to enhance diabetic wound healing, the precise mechanisms remain unclear. ADSCs-EVs were isolated via ultracentrifugation and characterized through transmission electron microscopy, Western blot, and nanoparticle tracking analysis. Their effects on human umbilical vein endothelial cells (HUVECs) and RAW 264.7 macrophages were assessed in vitro, focusing on cell proliferation, migration, tube formation, and macrophage polarization. A diabetic rat wound model was used to evaluate their therapeutic impact on wound healing and angiogenesis, with histological and immunofluorescence analyses. mRNA sequencing identified Cellular communication network factor 2(CCN2) as a key upregulated gene, leading to further exploration of its role in ADSCs-EVs-mediated angiogenesis and wound healing via the PI3K/AKT pathway. Gene silencing (si-CCN2) and pharmacological inhibition (LY294002) were employed both in vitro and in vivo. ADSCs-EVs were successfully isolated and characterized. In vitro, ADSCs-EVs promoted HUVEC proliferation, migration, and tube formation, and facilitated macrophage polarization to the M2 phenotype. In vivo studies using a diabetic rat wound model confirmed the pro-healing effects of ADSCs-EVs, including enhanced angiogenesis, granulation tissue formation, and accelerated wound closure. mRNA sequencing revealed that CCN2 expression was significantly upregulated in diabetic wound tissues treated with ADSCs-EVs. Further experiments showed that inhibiting CCN2 expression (si-CCN2) or blocking the PI3K/AKT pathway (LY294002) partially suppressed HUVEC proliferation, migration, tube formation, and angiogenesis, and counteracted the pro-healing effects of ADSCs-EVs. ADSCs-EVs promote diabetic wound healing through the CCN2/PI3K/AKT pathway, offering a promising therapeutic target for diabetic wound repair.

Ischemia is a significant factor affecting the repair of peripheral nerve injuries, while exosomes have been shown to promote angiogenesis. To further investigate the detailed processes and efficacy of exosome thera & hybull; py for ischemic peripheral nerve injuries, this study utilized glucose-modified near-infrared-II (NIR-II) quantum dots (QDs) to label adipose-derived stem cell exosomes (QDs-ADSC-Exos), enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage. Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes, with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo. Notably, QDs-ADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage. Func & hybull; tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration. This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio & hybull; temporal characteristics of exosome therapy, providing objective evidence for the further optimization of exosome-based treatment protocols.

Lymphatic contractile functions are crucial for understanding the regulatory role of the lymphatic system and the pathogenesis of lymphovascular diseases. The second near-infrared window (NIR-II) imaging provides exceptional spatial resolution and real-time capabilities for the quantitative analysis of lymphatic contractile functions. However, current methods for assessing lymphatic contractile function are manual and subjective. In this study, we propose an automated assessment approach that segments lymphatic vessels using the Top-hat transform and Frangi filter, and selects regions of interest (ROIs) based on lymphatic morphological features and flow properties in NIR-II images. This method accurately quantifies contraction-related parameters, including frequency and velocity. Experiments demonstrated precise segmentation and reliable extraction of contractile parameters. Specifically, in different areas, contraction frequencies were measured at 1.37, 1.01, 2.58, and 2.14 contractions per minute, while propulsion velocities reached 3.57, 4.81, 0.43, and 4.25 pixels per second, illustrating the method’s capability to detect regional variations in lymphatic function. The proposed approach enables automated, rapid, and quantitative analysis of lymphatic contraction frequency and velocity, offering a promising tool for evaluating lymphatic function and aiding in the clinical diagnosis of lymphatic diseases.

Body donation is a valuable resource in medical education, research, clinical diagnosis, and treatment. Consequently, donors are honored as "Silent Mentors" in Chinese medical schools. This article briefly reviews the history, current status, and strategies to promote body donation in China (excluding data from Hong Kong, Macao, and Taiwan regions) and discusses the problems encountered in body donation work in China. After establishing the People's Republic of China in 1949, the central government issued regulations on the use of dissected bodies. In 2001, the "Shanghai Regulations on Body Donation" were officially implemented and became China's first local legislative regulation on body donation. Subsequently, local legislative regulations and rules on body donation were issued in various regions to promote smooth and orderly body donation. There has been tremendous development in body donation in China for more than 40 years; however, the progress of this partial work has been uneven in various areas owing to the influence of traditional ethical concepts. It is, therefore, imperative to legislate body donations at a national level. Raising the public's scientific literacy and changing the traditional concept of funerals can create a positive social atmosphere for body donation, thus increasing the public's awareness and willingness to donate their bodies. Donating the body at the end of life contributes to life science and medical causes and is a noble act worthy of praise.

BACKGROUND:Pathological scars (PS) are one of the most common complications in patients with trauma and burns, leading to functional impairments and aesthetic concerns. Mechanical tension at injury sites is a crucial factor in PS formation. However, the precise mechanisms remain unclear due to the lack of reliable animal models. RESULTS:We developed a novel mouse model, the Retroflex Scar Model (RSM), which induces PS by applying controlled tension to wounds in vivo. RNA sequencing identified significant transcriptome changes in RSM-induced scars. Elevated expression of E-Selectin (Sele) was observed in endothelial cells from both the RSM model and human PS (Keloid) samples. In vitro studies demonstrated that cyclic mechanical stretching (CMS) increased Sele expression, promoting monocyte adhesion and the release of pro-inflammatory factors. Single-cell sequencing analysis from the GEO database, complemented by Western blotting, immunofluorescence, and co-immunoprecipitation, confirmed the role of Sele-mediated monocyte adhesion in PS formation. Additionally, we developed Sele-targeted siRNA liposome nanoparticles (LNPs) to inhibit monocyte adhesion. Intradermal administration of these LNPs effectively reduced PS formation in both in vivo and in vitro studies. CONCLUSIONS:This study successfully established a reliable mouse model for PS, highlighting the significant roles of mechanical tension and chronic inflammation in PS formation. We identified Sele as a key therapeutic target and developed Sele-targeted siRNA LNPs, which demonstrated potential as a preventive strategy for PS. These findings provide valuable insights into PS pathogenesis and open new avenues for developing effective treatments for pathological scars.

The administration time is a critical but long-neglected point in cell therapy based on macrophages because the incorrect time of macrophage administration could result in diverse outcomes regarding the same macrophage therapy. In this work, the second near-infrared (NIR-II) fluorescence imaging in vivo tracking of M2 macrophages during a pro-healing therapy in the mice model of rotator cuff injury revealed that the behavior of administrated macrophages was influenced by the timing of their administration. The delayed cell therapy (DCT) group had a longer retention time of injected M2 macrophages in the repairing tissue than that in the immediate cell therapy (ICT) group. Both Keller–Segel model and histological analysis further demonstrated that DCT altered the chemotaxis of M2 macrophages and improved the healing outcome of the repaired structure in comparison with ICT. Our results offer a possible explanation of previous conflicting results on reparative cell therapy and provoke reconsideration of the timing of these therapies.

Background Several surgeons have described studies of free-tissue transfers using veins instead of arteries. These innovative microsurgical techniques can offer several advantages, such as an easier dissection during flap harvesting, and represent an alternative during an accidental surgical mistake or development of new surgical procedures. The purpose of this study was to describe and explore different constructs of vascularized lymph node transfer (VLNT) only based on venous blood flow in a mouse model, evaluate their blood flow microcirculation through indocyanine green (ICG) angiography and investigate the lymphatic drainage function and the lymph nodes' structures. Methods Five types of venous lymph node flaps (LNF) were created and investigated: Types IA, IB, IC, IIA and IIB were developed by ICG intraoperatively (with videos in the article). Seven weeks later, by applying methylene blue, the recanalization of the lymphatic vessels between the LNF and the recipient site was detected. Lymph nodes were collected at the same time and their structures were analyzed by hematoxylin and eosin staining analysis. Results All of the venous LNFs developed except Type IC. Seven weeks later, methylene blue flowed into Types IA, IB, IIA and IIB from recipient sites. When comparing with arteriovenous lymph node, the medullary sinus was diffusely distributed in venous lymph nodes. The proportion of cells was significantly reduced (p < 0.05). The artery diameters were significantly smaller (p < 0.05). The veins diameters and lymphatic vessels output in Types IA, IB, IIA and IIB were more dilated (p < 0.05). Conclusions This research demonstrated that Type IA, IB, IIA and IIB venous LNFs can retrogradely receive venous blood supply; they can survive, produce a lymphatic recanalization and integrate with the surrounding tissue, despite lymph node structural changes. Our results will improve the understanding of the survival mechanism of venous LNFs and will help researchers to design new studies or lymphatic models and eventually find an alternative procedure for the surgical treatment of lymphedema.

解剖学是医学生的重要必修课,是医学教育的主干课程和不可动摇的基石.缺乏对器官与组织解剖结构的良好掌握和理解,医生无法开展有效的临床诊断和治疗[1].目前国内各医学院校,解剖学授课形式依旧以一对多的课堂教学为主,利用二维幻灯片演示解剖学的基本概念、形态结构和临床病例等[2].然而实际人体是三维立体的,仅通过二维图像学生很难理解各结构之间的空间位置及对应关系.此外,初学者需要一定时间适应通过空间想象理解解剖结构,具有挑战性[3-4].研究表明,医学生常难以从书籍或互联网上的二维图像中获得对三维解剖结构的充分空间理解[5-6].因此,传统解剖学二维的教学模式限制学习者对人体解剖学的准确认知和充分理解.

课程思政教育是将思想政治教育渗透到专业课程教学过程中,注重在价值传播中凝聚知识底蕴,在知识传播中强调价值引领,因此在高校思想政治工作中发挥了重要作用[1].解剖学课程因蕴含丰富的思政元素,成为培育医学生人文素养、科学精神和医者仁心的重要而独特的学科.现有解剖学课程思政教育内容充实、形式丰富,但更多的是以教师为主体对学生进行教育和输出,但课程思政教育对学生的影响,即学生对课程思政教育的获得感与满意度,尚欠缺有效的评价与探讨[2-4].

Advancements in lymphography technology are essential for comprehensive investigation of the lymphatic system and its function. Here, a shortwave infrared (SWIR) luminescence imaging of lymphatic vessels is proposed in both normal and lymphatic dysfunction in rat models with PbS quantum dots (PbS Qdots). The lymphography with PbS Qdots can clearly and rapidly demonstrate the normal lymphatic morphology in both the tail and hind limb. More importantly, compared to ICG, SWIR luminescence imaging with PbS Qdots can easily identify the dominant lymphatic vessel and node with higher luminescence signal in rats. Moreover, lymphatic pump is identified as segment contracting sections with a size of ≈1 cm in rat by in vivo SWIR lymphograhy, which propose a direct feature for precise evaluation of lymphatic function. Notably, in vivo SWIR luminescence imaging with PbS Qdots also clearly deciphers the in vivo pattern of morphological and function recovery from lymphatic system in rat model. In summary, SWIR luminescence imaging with PbS Qdots can improve the lymphography and thus deepen the understanding of the morphology and structure of the lymphatic system as well as lymphatic function such as lymphatic pump, which will facilitate the diagnosis of lymphatic dysfunction in the future.

BackgroundAutologous nerve grafting, the criterion standard for bridging peripheral nerves, can cause complications at the donor site. We investigated a novel approach to reconstruct the nerve gap with a split cross-sectional unmatched semifascicle autograft, which was harvested from the distal part of the injured nerve.MethodsA patient diagnosed with left-sided frontal branch facial nerve dissection underwent nerve bridging emergency surgery using a semifascicle nerve graft. A sciatic nerve model was used to validate the feasibility and mechanism of this method. Male Sprague-Dawley rats (n = 36) were randomized into (A) intact fascicle, (B) semifascicle, and (C) semifascicle + conduit groups and further subdivided into 4- and 8-week groups for histological analysis of the neurotissue area, fibers, and Schwann cells. The 8-week groups underwent weekly pain and temperature tests; the wet weight of the gastrocnemius muscle was measured after euthanasia.ResultsThe frontalis of the patient's injured side exhibited movement at 2 months postsurgery and recovered a symmetrical appearance at 13 months. Group A exhibited more neurotissue areas and fibers than groups B and C at week 4; group B had more neurotissue than group C. Group A had greater neurotissue areas than groups B and C at week 8; groups B and C exhibited no differences. The groups displayed no differences regarding nerve fiber, pain, and temperature analysis at week 8. Muscle wet weight of groups A and B exhibited no differences and was higher than that of group C.ConclusionWe demonstrated the clinical translational value of semifascicle nerve grafts; the injured site was both the donor and recipient, thereby avoiding donor site damage and associated complications.

Extracellular vesicles (EVs) show potential as a therapeutic tool for peripheral nerve injury (PNI), promoting neurological regeneration. However, there are limited data on the in vivo spatio-temporal trafficking and biodistribution of EVs. In this study, we introduce a new non-invasive near-infrared fluorescence imaging strategy based on glucose-conjugated quantum dot (QDs-Glu) labeling to target and track EVs in a sciatic nerve injury rat model in real-time. Our results demonstrate that the injected EVs migrated from the uninjured site to the injured site of the nerve, with an increase in fluorescence signals detected from 4 to 7 days post-injection, indicating the release of contents from the EVs with therapeutic effects. Immunofluorescence and behavioral tests revealed that the EV therapy promoted nerve regeneration and functional recovery at 28 days post-injection. We also found a relationship between functional recovery and the NIR-II fluorescence intensity change pattern, providing novel evidence for the therapeutic effects of EV therapy using real-time NIR-II imaging at the live animal level. This approach initiates a new path for monitoring EVs in treating PNI under in vivo NIR-II imaging, enhancing our understanding of the efficacy of EV therapy on peripheral nerve regeneration and its mechanisms.

The degradation of collagen in different body parts is a critical point for designing collagen-based biomedical products. Here, three kinds of collagens labeled by second near-infrared (NIR-II) quantum dots (QDs), including collagen with low crosslinking degree (LC), middle crosslinking degree (MC) and high crosslinking degree (HC), were injected into the subcutaneous tissue, muscle and joints of the mouse model, respectively, in order to investigate the in vivo degradation pattern of collagen by NIR-II live imaging. The results of NIR-II imaging indicated that all tested collagens could be fully degraded after 35 days in the subcutaneous tissue, muscle and joints of the mouse model. However, the average degradation rate of subcutaneous tissue (k = 0.13) and muscle (k = 0.23) was slower than that of the joints (shoulder: k = 0.42, knee: k = 0.55). Specifically, the degradation rate of HC (k = 0.13) was slower than LC (k = 0.30) in muscle, while HC showed the fastest degradation rate in the shoulder and knee joints. In summary, NIR-II imaging could precisely identify the in vivo degradation rate of collagen. Moreover, the degradation rate of collagen was more closely related to the implanted body parts rather than the crosslinking degree of collagen, which was slower in the subcutaneous tissue and muscle compared to the joints in the mouse model.

在线课程教育已成为信息时代的新型教育模式,但目前缺乏正式统一且规范的在线课程建设的标准化流程.本文探索了医学形态学在线课程建设的标准化流程的制定,体现"医学生掌握课程为中心"的理念,明确形态学在线课程学习预期目标建立、学习活动与实践、形态学标本使用以及在线课程学习有效性评估之间的建设步骤设想,提出具有一定操作性、内容科学、结构合理的本土化在线课程建设流程,作为可供参考的医学形态学在线课程建设指南,推动并完善我国在线教育规范化和高质量发展.

Keloids are an abnormal fibroproliferative wound-healing disease with a poorly understood pathogenesis, making it difficult to predict and prevent this disease in clinical settings. Identifying disease-specific signatures at the molecular and cellular levels in both the blood circulation and primary lesions is urgently needed to develop novel biomarkers for risk assessment and therapeutic targets for recurrence-free treatment. There is mounting evidence of immune cell dysregulation in keloid scarring. In this study, we aimed to profile keloid scar tissues and blood cells and found that downregulation of cytotoxic CD8+ T cells is a keloid signature in the peripheral blood and keloid lesions. Single-cell RNA sequencing revealed that the NKG2A/CD94 complex was specifically upregulated, which might contribute to the significant reduction in CTLs within the scar tissue boundary. In addition, the NKG2A/CD94 complex was associated with high serum levels of soluble human leukocyte antigen-E (sHLA-E). We subsequently measured sHLA-E in our hospital-based study cohort, consisting of 104 keloid patients, 512 healthy donors, and 100 patients with an interfering disease. The sensitivity and specificity of sHLA-E were 83.69% (87/104) and 92.16% (564/612), respectively, and hypertrophic scars and other unrelated diseases exhibited minimal interference with the test results. Furthermore, intralesional therapy with triamcinolone combined with 5-fluorouracil drastically decreased the sHLA-E levels in keloid patients with better prognostic outcomes, while an incomplete reduction in the sHLA-E levels in patient serum was associated with higher recurrence. sHLA-E may effectively serve as a diagnostic marker for assessing the risk of keloid formation and a prognostic marker for the clinical outcomes of intralesional treatment.

BACKGROUND:Peripheral nerve regeneration is a coordinated process of Schwann cell (SC) reprogramming and intrinsic neuronal growth program activation. Panaxydol (PND) is a strong biologically active traditional Chinese medicine monomer extracted from Panax notoginseng rhizomes. In vitro, PND protects neurons and SCs from injury and stimulates the expression and secretion of neurotrophic factors (NTFs) by SCs. We hypothesized that PND may also promote peripheral nerve regeneration in adult animals.METHODS:PND (10 mg/kg body weight) was injected intraperitoneally into the Sprague-Dawley (SD) rats for two consecutive weeks after sciatic nerve transection. The morphology of the repaired sciatic nerve was evaluated after 16 weeks, and sensory and motor function recovery was evaluated using functional and behavioral techniques.RESULTS:PND was biologically safe at an injection dose of 10 mg/kg/day. After 14 days, it significantly increased the myelination of regenerated nerve fibers, and promoted sensory and motor function recovery. In the early stage of injury, PND significantly upregulated the mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptors in distal injured nerves, which may represent a possible mechanism by which PND promotes nerve regeneration in vivo.CONCLUSIONS:Our study demonstrated that PND leads to sensory and motor recovery in a sciatic nerve transection model rat. Furthermore, we showed that BDNF mRNA level was significantly increased in the injured distal nerve, potentially contributing to the functional recovery. Further research is warrantied to examine whether direct injection is a more efficient method to increase BDNF expression compared to an exogenous BDNF administration.

The treatment of hypertrophic scar (HS) has thus far been a clinical challenge. We evaluated the therapeutic effect of CO2 fractional laser combined with 5-fluorouracil ethosomal gel (5-FU EG) in rabbit HS model. HS model was established as standardized scars on the ventral surface of rabbit ears, divided into four groups: control (no intervention), EG treatment, laser treatment, and combined treatment group (laser plus 5-FU EG). Clinical macroscopic and H&E-stained microscopic observations were conducted to assess HS improvement. The mRNA levels of types I and III collagen, transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6) were detected by real-time PCR. After 14 days, H&E staining shows that the thickness of HS in treatment groups was significantly lower compared with the control group, and the thickness in laser treatment group and combined treatment group was significantly lower compared with the EG treatment group. The mRNA levels of types I and III collagen, TGF-β1 were significantly low in all treatment groups, whereas IL-6 was highest in the laser treatment group at day 14. The macro- and microscopic effects of the combined and CO2 fractional laser treatment were better compared with 5-FU EG only. Inhibition of types I and III collagen, TGF-β1 are the possible underlying mechanism of action, whereas the function of IL-6 remains to be further studied. Our study suggests that the effect of combined 5-FU EG and laser, as well as laser-only treatment are superior to 5-FU EG monotreatment. The mechanism of HS improvement is related to reduction of collagen I/III and the inhibition of TGF-β1 expression.

AIMS:Engineered conduction tissues (ECTs) fabricated from cardiac progenitor cells (CPCs) and collagen sponges were precisely targeted for the treatment of atrioventricular conduction block in our previous studies. However, obvious shrinkage and deformation of ECTs was observed during in vitro culture. According to the literature, it can be speculated that basic fibroblast growth factor (bFGF) may downregulate alpha-smooth muscle actin (α-SMA) produced by CPCs to prevent the shrinkage of CPC-engineered conduction tissues.MAIN METHODS:In this study, culture media with or without bFGF were used for both cell culture and 3D tissue construction. The expression of α-SMA and the size change of engineered tissue were analyzed to evaluate the feasibility of adding bFGF to regulate α-SMA expression and shrinkage of constructs. In addition, cardiac-specific examinations were performed to evaluate the effect of bFGF on cardiac tissue formation.KEY FINDINGS:Supplementation with bFGF efficiently relieved shrinkage of engineered tissue by downregulating the expression of α-SMA at both the cellular and 3D tissue levels. Moreover, bFGF had a positive influence on cardiac tissue formation in terms of cell viability, tissue organization and electrical conduction velocity.SIGNIFICANCE:This study provides a guide for both shape control and quality improvement of CPC-engineered cardiac tissues.