Abnormal iron metabolism is closely linked to sarcopenia; however, the specific iron metabolism features of fat-infiltrating sarcopenia remain poorly understood. Proteomic sequencing revealed that in skeletal muscle with severe fat infiltration, the expression of iron utilization-related proteins was significantly downregulated, whereas that of iron uptake and storage proteins was markedly upregulated, thereby presenting an abnormal iron deficiency (ID) phenotype. Nevertheless, the mechanism by which ID drives intramuscular fat infiltration has not been fully elucidated. Using clinical samples, aged murine ID models, and in vitro cell assays, this study is the first to demonstrate that ID stabilizes hypoxia-inducible factor-1α (HIF-1α), promoting aberrant adipogenic differentiation of fibro-adipogenic progenitors (FAPs), disrupting the homeostatic balance between satellite cells (SCs) and FAPs, exacerbating skeletal muscle fat infiltration, and impairing muscle repair capacity. Notably, treatment with the HIF-1α inhibitor PX478 reversed these pathological alterations and improved muscle function. Collectively, our findings identify the ID-HIF-1α-FAPs axis as a key driver of intramuscular fat infiltration, offering a novel therapeutic target for the clinical management of fat-infiltrating sarcopenia. ### Competing Interest Statement The authors have declared no competing interest. National Natural Science Foundation of China, 82371957, 82502990 Beijing Natural Science Foundation, 7254373 Beijing Physician Scientist Training Project, BJPSTP-2024-08 Beijing Jishuitan Research Funding, JSTYC202207 CMU Talent Project, A2413 Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes, JYY2023-8, JYY2023-11 Beijing Municipal Health Commission, BJRITO-RDP Cultivation Project of Natural Science Foundation, Beijing Jishuitan Hospital, Capital Medical University, ZR-202407
Skeletal muscle injury repair involves dynamic immune cell regulation, yet how exercise modulates this process remains unclear. This study investigated the impact of swimming training on immune cell spatiotemporal dynamics, fat infiltration, and muscle regeneration in glycerol-injured mouse gastrocnemius muscles. Swimming training accelerated functional recovery (grip strength, rotarod endurance, gait mechanics) and reduced serum creatine kinase activity, indicating mitigated muscle damage. Histological analysis revealed that swimming decreased collagen deposition and fat infiltration while promoting myofiber regeneration. Mechanistically, swimming induced early (days 1–3 post-injury) increases in natural killer cells, granulocytes, monocytes, macrophages, and M1 macrophages, initiating inflammatory responses for necrotic tissue clearance. From days 3–7, M2 macrophage numbers rose significantly, facilitating satellite cell differentiation. Concurrently, swimming promoted recruitment of regulatory T (Treg) cells and fibro-adipogenic progenitors (FAPs), particularly IL-33+FAPs, driving the immune microenvironment from pro-inflammatory to anti-inflammatory states. Cytokine profiling showed transient elevation of pro-inflammatory factors (TNF-α, IL-6) in the acute phase, followed by anti-inflammatory IL-10 upregulation during repair. Transcriptomic analysis validated spatiotemporal gene expression shifts, including enhanced Treg cell chemotaxis and suppressed adipogenesis. These findings demonstrate that swimming training optimizes muscle repair by orchestrating immune cell dynamics and cytokine networks, highlighting its potential as a therapeutic strategy to mitigate fat infiltration and enhance regeneration in injured muscle.
In recent years, multi-lineage muscle organoids have rapidly emerged as transformative research tools, providing high-fidelity models for deciphering skeletal muscle development and the pathological mechanisms of muscle diseases such as sarcopenia, amyotrophic lateral sclerosis, and myasthenia gravis. Primarily derived from pluripotent stem cells, these organoids integrate multiple functional lineages, such as skeletal muscle, neural, vascular, and skeletal components, thereby addressing the limitations of conventional single-tissue muscle models. In parallel, multi-organoid systems, such as assembloids and organ-on-a-chip platforms, further integrate distinct organoids (e.g., muscle, skeletal tissue, tendon, and hindbrain/cervical spinal cord) to reconstruct inter-organ communication and systemic physiology under physiologically relevant conditions. By recapitulating in vivo-like multi-tissue interactions, they serve as critical platforms for drug screening and therapeutic development. This review summarizes recent advances in multi-lineage muscle organoids and multi-organoid systems, outlining their cellular sources, construction strategies, and major applications in basic research, disease modeling, and drug discovery, and discusses current challenges and future directions to enhance their potential in muscle research.
Intervertebral disc degeneration (IDD) is the most common and critical pathological basis for various spinal disorders. In this study, we investigated how plasminogen activator urokinase (PLAU) promotes IDD progression through the HIPPO pathway. Bioinformatics analysis showed that PLAU is a hub gene in IDD. Both in vitro and in vivo experiments confirmed that PLAU can promote the apoptosis of nucleus pulposus chondrocytes. PLAU activates the HIPPO signaling pathway by increasing the phosphorylation levels of mammalian ste20-like kinases 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes associated protein (YAP), promoting chondrocyte apoptosis, which is one of the reasons for the accelerated progression of IDD. These findings provide new insights into the role of PLAU in IDD and highlight its potential as a therapeutic target for IDD.
Macrophages are key innate immune cells in the muscle environment of sarcopenia patients, significantly influencing muscle stem cell (MuSC) proliferation and differentiation. However, prolonged activation of macrophages can hinder muscle recovery. In this study, it synthesizes lipoic acid-modified gold nanoparticles (LA-Au NPs) of varying sizes to evaluate their biocompatibility and immunomodulatory effects. The findings demonstrate that LA-Au NPs exhibit excellent biocompatibility with macrophages and promoted M2 polarization in a size-dependent manner. Mechanistically, LA-Au NPs facilitated metabolic reprogramming in macrophages by enhancing lysosomal autophagy and mitochondrial oxidative phosphorylation. Furthermore, macrophages are shown to chemotax toward MuSCs, regulating their proliferation via the chemokine system, inhibiting MuSC apoptosis, and enhancing differentiation under inflammatory conditions. In vivo studies have confirmed the safety and efficacy of LA-Au NPs in sarcopenia mice. To further enhance the effectiveness of LA-Au NPs, it investigates a delivery strategy that involves preconditioning macrophages with LA-Au NPs (Mac@Au NPs). Compared to the direct injection of LA-Au NPs, Mac@Au NPs demonstrate significantly greater benefits for muscle repair. This highlights the potential of macrophage therapy as a promising strategy for effective muscle regeneration and therapeutic intervention in sarcopenia.
ABSTRACTObjectiveUnilateral biportal endoscopic discectomy (UBE) is an emerging and minimally invasive surgeryfor lumbar spinal degenerative disease. However, the efficacy, safety and the radiological changes of dural sac and paraspinal muscle of UBE compared with the conventional percutaneous transforaminal endoscopic discectomy (PTED) remains to be determined. The purpose of the study was to comprehensively compare the clinical efficacy between UBE and PTED in the surgical treatment of lumbar spinal degenerative disease.MethodsThe clinical and radiological data of patients who underwent single‐segment endoscopic surgery for lumbar spinal degenerative disease in our hospital from January 2021 to June 2022 were collected in the retrospective study. The visual analogue score (VAS) for back and leg pain, Oswestry disability index (ODI) before and 3, 6, and 12 months postoperative, changes of the cross‐sectional area of the dural sac area and paraspinal muscles on axial T2‐weighted MRI, operation time, intraoperative complications, MacNab criteria for evaluating efficacy at 12 months postoperatively, and recurrence rate of symptoms within 12 months were compared between patients undergoing PTED and UBE surgeries.ResultsA total of 142 patients were included. Among them 74 patients underwent PTED surgery, and 68 patients underwent UBE surgery. No statistically significant differences were identified between the groups in demographic variables. The average VAS and ODI scores in both groups showed significant improvement during the follow‐up but without statistically significant difference between the groups. The average operation time in the PTED group was 74.82 ± 19.49 min shorter than the 81.36 ± 21.37 min in the UBE group, exhibiting no statistically significant difference. Although the incidence of complications and recurrence was lower in the UBE group (4.05% vs. 1.47%, p = 0.354; 4.05% vs. 1.47%, p = 0.354, respectively), these differences did not reach statistical significance. The dural sac area in the PTED group increased byan average of 43.16 ± 14.62 cm2, and it was 68.53 ± 16.42 cm2 in the UBE group. Despite the dural sac area increased in both groups, the UBE group had a statistically significant greater improvement than the PTED group (p = 0.000). The area of the paraspinal muscle in the UBE group was significantly greater postoperatively (34.54 ± 2.75 cm2 vs. 36.22 ± 2.96 cm2, p = 0.001) and significantly less than in the PTED group at 12 months postoperatively (31.17 ± 2.59 cm2 vs. 29.46 ± 3.11 cm2, p = 0.001).ConclusionBoth PTED and UBE surgeries can achieve satisfactory improvement in symptoms and function for patients with lumbar spinal degenerative disease and can be well‐maintained as a first‐line minimally invasive treatment. However, the UBE technique can achieve a better decompression area to restore the normal shape of the dural sac but may lead to greater paraspinal muscle damage and atrophy.
The association of short-term ambient air pollution exposure with osteoarthritis (OA) outpatient visits has been unclear and no study has assessed the modifying roles of district-level characteristics in the association between ambient air pollution exposure and OA outpatient visits. We investigated the cumulative associations of ambient air pollution exposure with daily OA outpatient visits and vulnerable factors influencing the associations using data from 16 districts of Beijing, China during 2013-2019. A total of 18,351,795 OA outpatient visits were included in the analyses. An increase of 10 mu g/m(3) in fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), maximum 8-hour moving-average ozone (8 h-O-3), and 0.1 mg/m(3) in carbon monoxide (CO) at representative lag days were associated with significant increases of 0.31 %, 0.06 %, 0.77 %, 0.87 %, 0.30 %, and 0.48 % in daily OA outpatient visits, respectively. Considerable OA outpatient visits were attributable to short-term ambient air pollution exposure. In addition, low temperature and high humidity aggravated ambient air pollution associated OA outpatient visits. District-level characteristics, such as population density, green coverage rate, and urbanization rate modified the risk of OA outpatient visits associated with air pollution exposure. These findings highlight the significance of controlling ambient air pollution during the urbanization process, which is useful in policy formation and implementation.
Large full-thickness skin lesions have been one of the most challenging clinical problems in plastic surgery repair and reconstruction. To achieve in situ skin regeneration and perfect clinical outcomes, we must address two significant obstacles: angiogenesis deficiency and inflammatory dysfunction. Recently, black phosphorus has shown great promise in wound healing. However, few studies have explored the bio-effects of BP to promote in situ skin regeneration based on its nanoproperties. Here, to investigate whether black phosphorus nanosheets have positive bio-effects on in situ skin repair, we verified black phosphorus nanosheets' positive effects on angiogenic and anti-inflammatory abilities in vitro. Next, the in vivo evaluation performed on the rat large full-thickness excisional wound splinting model more comprehensively showed that the positive bio-effects of black phosphorus nanosheets are multilevel in wound healing, which can effectively enhance anti-inflammatory ability, angiogenesis, collagen deposition, and skin re-epithelialization. Then, multiomics analysis was performed to explore further the mechanism of black phosphorus nanosheets' regulation of endothelial cells in depth. Molecular mechanistically, black phosphorus nanosheets activated the JAK-STAT-OAS signaling pathway to promote cellular function and mitochondrial energy metabolism in endothelial cells. This study can provide a theoretical basis for applying two-dimensional black phosphorus nanosheets as nanomedicine to achieve in situ tissue regeneration in complex human pathological microenvironments, guiding the subsequent optimization of black phosphorus.
Although the knee joint (KNJ) and temporomandibular joint (TMJ) all belong to the synovial joint, there are many differences in developmental origin, joint structure and articular cartilage type. Studies of joint development in embryos have been performed, mainly using poultry and rodents. However, KNJ and TMJ in poultry and rodents differ from those in humans in several ways. Very little work has been done on the embryonic development of KNJ and TMJ in large mammals. Several studies have shown that pigs are ideal animals for embryonic development research. Embryonic day 30 (E30), E35, E45, E55, E75, E90, Postnatal day 0 (P0) and Postnatal day 30 (P30) embryos/fetuses from the pigs were used for this study. The results showed that KNJ develops earlier than TMJ. Only one mesenchymal condensate of KNJ is formed on E30, while two mesenchymal condensates of TMJ are present on E35. All structures of KNJ and TMJ were formed on E45. The growth plate of KNJ begins to develop on E45 and becomes more pronounced from E55 to P30. From E75 to E90, more and more vascular-rich cartilage canals form in the cartilage regions of both joints. The cartilaginous canal of the TMJ divides the condyle into sections along the longitudinal axis of the condyle. This arrangement of cartilaginous canal was not found in the KNJ. The chondrification of KNJ precedes that of TMJ. Ossification of the knee condyle occurs gradually from the middle to the periphery, while that of the TMJ occurs gradually from the base of the mandibular condyle. In the KNJ, the ossification of the articular condyle is evident from P0 to P30, and the growth plate is completely formed on P30. In the TMJ, the cartilage layer of condyle becomes thinner from P0 to P30. There is no growth plate formation in TMJ during its entire development. There is no growth plate formation in the TMJ throughout its development. The condyle may be the developmental center of the TMJ. The chondrocytes and hypertrophic chondrocytes of the growth plate are densely arranged. The condylar chondrocytes of TMJ are scattered, while the hypertrophic chondrocytes are arranged. Embryonic development of KNJ and TMJ in pigs is an important bridge for translating the results of rodent studies to medical applications.
To learn about advances in skeletal muscle tissue engineering (SMTE) in recent years, we used VOSviewer and Citespace software to quantitatively analyze and visualize relevant literature in the Web of Science database during the period 2012-2022. By mapping high-frequency keyword relationship networks, keyword time zones, and journal article cocitations, we clarified the areas of great interest, evolutionary paths, and developmental trends in research on SMTE. We conducted an in-depth analysis of highly cited and representative articles at various stages to summarize the mainstream research areas of great interest in SMTE and discussed the future development and challenges in this field, intending to provide a reference for the clinical treatment of skeletal muscle injury repair. We found that a collaborative network of authors has formed in this field; the journals publishing SMTE articles belong to the fields of biomaterials and tissue engineering, and open-access journals have played a key role in the promotion of the development of SMTE; and in the past decade, there has been rapid progress in SMTE research in terms of both depth and breadth.Impact statement Compared with the literature review method, bibliometrics can provide a comprehensive knowledge of a knowledge area based on a huge amount of literature. In this article, based on the Web of Science database, CiteSpace, and Vosviewer visualization tools were used to measure and analyze the literature reports in the field of skeletal muscle tissue engineering (SMTE). The research hotspots and cutting-edge information on SMTE were mined in terms of the number of publications, the number of citations, the keywords, the authors, and the publishing institutions to understand the current status of the research on SMTE in the world, to provide a reference for related researchers, engineering research in the field of SMTE, to comprehensively understand the current status of global research in the field of SMTE, and to provide a reference for related researchers.
Objective:To investigate short-term effectiveness of robot-guided femoral neck system (FNS) combined with cannulated compression screw (CCS) fixation in treatment of femoral neck fracture in young and middle-aged patients. Methods:A clinical data of 49 young and middle-aged patients with femoral neck fractures, who met the selection criteria and admitted between January 2021 and June 2023, was retrospectively analyzed. After reduction of femoral neck fractures, 27 cases were treated with robot-guided FNS fixation (FNS group) and 22 cases with robot-guided FNS and CCS fixation (FNS+CCS group). There was no significant difference in baseline data such as gender, age, cause of fracture, time from fracture to operation, fracture side, and classification (Garden classification and Pauwels classification) between the two groups ( P>0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, the time when the patient began bearing weight, and hip joint pain and functional scores (VAS score and Harris score) at last follow-up for two groups were recorded. Imaging re-examination was taken to evaluate the quality of fracture reduction, fracture healing, as well as the occurrence of fracture non-union, osteonecrosis of the femoral head, and femoral neck shortening. Results:All operations were successfully completed and the incisions healed by first intention. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05), and the intraoperative fluoroscopy frequency in FNS+CCS group significantly increased compared to FNS group ( P<0.05). All patients were followed up 12-18 months (mean, 14.1 months). Imaging re-examination showed that there was no significant difference in fracture reduction quality between the two groups ( P>0.05), but the fracture healing time was significantly shorter in FNS+CCS group than in FNS group, and weight-bearing began earlier ( P<0.05). The incidences of femoral neck shortening, fracture non-union, and osteonecrosis of the femoral head were lower in FNS+CCS group than in FNS group, and there was significant difference in the incidence of femoral neck shortening between groups ( P<0.05). At last follow-up, there was no significant difference in VAS scores between the two groups ( P>0.05). However, the Harris score was significantly higher in FNS+CCS group than in FNS group ( P<0.05). Conclusion:Compared with FNS fixation alone, robot-guided FNS combined with CCS fixation in the treatment of femoral neck fractures in young and middle-aged patients has obvious advantages in terms of early weight bearing and fracture healing, improves fracture healing rate, effectively prevents postoperative complications, and can obtain good short-term effectiveness.
Recent studies found the intrusion and retention of exogenous fine particles into joints, but epidemiological data for long- and intermediate-term exposure associations are scare. Here, all urban working, retired employee, and rural residents (16.78 million) in Beijing from January 1, 2011 to December 31, 2019 were included to investigate the effects of long- and intermediate-term ambient particulate exposure on development of osteoarthritis. We identified 1,742,067 participants as first-visit patients with osteoarthritis. For each interquartile range increase in annual PM2.5 (23.32 mu g/m(3)) and PM10 (23.92 mu g/m(3)) exposure concentration, the pooled hazard ratios were respectively 1.238 (95% CI: 1.228, 1.249) and 1.178 (95% CI: 1.168, 1.189) for first osteoarthritis outpatient visits. Moreover, age at first osteoarthritis outpatient visits significantly decreased by 4.52 (95% CI: 3.45 to 5.40) days per mu g/m(3) for annual PM2.5 exposure at below 67.85 mu g/m(3). Finally, among the six constituents analyzed, black carbon appears to be the most important component associated with the association between PM2.5 exposure and the three osteoarthritis-related outcomes.
Studies on the relationships between metal mixtures exposure and cognitive impairment in elderly individuals are limited, particularly the mechanism with metabolite. Few studies are available on the potential sex and age specific associations between metal exposure, metabolites and cognitive impairment. We examined plasma metal and blood metabolite concentrations among 1068 urban elderly participants. Statistical analysis included a battery of variable selection approaches, logistic regression for metal/metabolite associations, and Bayesian kernel machine regression (BKMR) to identify mixed effects of metals/metabolites on cognitive impairment risk. Our results showed that As was positively associated with cognitive impairment in the female (OR 95 % CI = 2.21 (1.36, 3.57)) and 60- to 70-year-old (OR 95 % CI = 2.60 (1.54, 4.41)) groups, Cr was positively associated with cognitive impairment in the male (OR 95 % CI = 2.15 (1.27, 3.63)) and 60- to 70-year-old (OR 95 % CI = 2.10 (1.24, 3.57)) groups, and Zn was negatively associated with cognitive impairment, especially in the female (OR 95 % CI = 0.46 (0.25, 0.84)), 60- to 70-year-old (OR 95 % CI =0.24 (0.12, 0.45)) and ≥ 80-year-old (OR 95 % CI = 0.19 (0.04, 0.86)) groups. Positive associations were observed between combined metals (Cr, Cu and As) and cognitive impairment, but Zn alleviated this tendency, especially in elderly individuals aged ≥80 years. Negative associations were observed between metabolites and cognitive impairment, especially in male, female and 60-70 years old groups. The mediation effects of metabolites on the association between metal exposure and cognitive impairment were observed, and the percentages of these effects were 15.60 % (Glu-Cr), 23.00 % (C5:1-Cu) and 16.36 % (Glu-Zn). Cr, Cu, and Zn could increase cognitive impairment risk through the "Malate-Aspartate Shuttle", "Glucose-Alanine Cycle", etc., pathways. Overall, we hypothesize that metabolites have mediation effects on the relationship between multi-metal exposure and cognitive impairment and that there are sex and age differences.
Objective: We analyzed quantitative computed tomography (CT) and chemical shift-encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots. Methods: In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2-L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements. Results: Of the 168 men, 29% had normal BMI (<24.0 kg/m(2)), 47% had overweight (24.0-27.9 kg/m(2)), and 24% had obesity (>= 28.0 kg/m(2)). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes. Conclusions: Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT.
Optimal planning of the pedicle screw path is a key guarantee of safe operation during the pedicle screw placement surgery. Existing semi-automatic or automatic path planning methods are mainly based on anatomical information of the vertebrae rather than mechanical information. If the biomechanical information that traditionally obtained through finite element analysis (FEA) could be incorporated into the automatic path planning procedure, it is promising to increase the clinical rationality of the planned surgical path and to reduce the risk of potential surgical failure. FEA is complex and computationally time-consuming, so it is difficult to directly apply the biomechanical information obtained from FEA to path planning. As the neural networks have nonlinear mapping capability to compute and predict complex features, this paper designs a two-stage automatic path planning method incorporating CT anatomical information with biomechanical information. In the first stage, the pre-processed CT images with the stress values obtained from the FEA are fed into the mechanical distributions generating subnetwork (MDGS) for training. In the second stage, CT images, the output of the MDGS and path (entry and directional points) are fed into the path points location subnetwork (PPLS). Finally, the initial paths that obtained from the PPLS are post-processed by the entry point relocating module (EPRM). The normalized mean absolute error (NMAE) of the stress values is 0.555%. The average mean squared error (MSE) of the relocated entry points and directional points are 2.61 and 2.851 voxels, respectively. The results demonstrate the effectiveness of the planned surgical path.
Radial extracorporeal shockwave therapy (rESWT) is a noninvasive medical technique that treats a range of musculoskeletal conditions. To understand its biological effects and develop personalized treatment plans, it is crucial to fully characterize the acoustic field that rESWT generates. This study presents a quantitative assessment of rESWT's acoustic field, achieved through experiments and simulations. The study measures the acoustic fields using a needle-type hydrophone under different machine settings and establishes and calibrates a computational model based on the experimental measurements. The study also determines the spatial distributions of peak pressure and energy flux density for different driving pressures. High-speed photography is used to visualize cavitation bubbles, which correspond to the negative pressure distribution. The study finds that the axial pressure distribution is similar to the acoustic radiation from an oscillating circular piston, whereas the radial pressure distribution cannot be described by acoustic radiation. Furthermore, the study develops a machine learning model that predicts positive pressure distributions for continuous driving pressure. Overall, this study expands our understanding of the acoustic fields generated by rESWT and provides quantitative information to explore underlying biological mechanisms and determine personalized treatment approaches.
Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.
目的 评估常见临床因素对术中基于CT自动配准的主动红外线光学导航系统临床精度的影响.方法 在临床手术室环境下,以腰椎等比例Sawbone模型作为体模,采用标准手术体位和设备位置,以3D NAV导航系统的术中CT自动配准导航模式模拟临床导航操作验证多种临床因素对导航精度的影响.模型表面嵌入多枚钛合金标记珠,使用导航软件分别测量钛珠在CT图像中和导航系统中的坐标,计算坐标距离作为导航临床精度.然后在无影灯照射、手术床位姿、导航相机位姿三种临床因素下测量导航临床精度,并与初始状态的精度比较.结果 初始状态导航临床精度为 0.64 mm±0.30 mm;无影灯照射手术区后,导航临床精度为0.63 mm±0.25 mm;手术床降低10 cm和左倾15°时,导航临床精度分别为0.61 mm±0.21 mm和 0.63 mm±0.21 mm;相机分别向左侧和向上旋转到示踪器恰好可见的位置时,导航临床精度分别为0.65 mm±0.30 mm和 0.62 mm±0.21 mm;相机分别移动到距示踪器 1m和2m的位置时,导航临床精度分别为0.64 mm±0.24 mm和 0.67 mm±0.28 mm.在各因素影响下该导航系统的临床精度均与初始状态无显著性差异(n=108,P>0.05).合并全部 864 次测量的导航临床精度为0.64 mm±0.25 mm.结论 本研究中的导航系统临床精度不受无影灯照射、手术床位姿和导航相机位姿的影响.
Robotic assistance in extracorporeal shock wave therapy (ESWT) has drawn attention in orthopedics for its automated operation instead of the time-lasting manual operation of physician, which dramatically alleviates the operation intensity of medical staff. It should be noticed that the dexterous operation in the small working space around the treatment site is an essential step for robotic ESWT. Considering the inverted cone shape of the working space around the treatment site in ESWT, this paper proposes and simulates a 3-DOFs robotic end-effector scheme with dual RCMs. A mechanism with PRR-type is determined which working space of $200 * 200 * 100 \mathrm{~mm}^{3}$ is verified through forward and inverse kinematic analysis. A $\Pi$-shaped structure is designed for rigidly connecting two RCM units which realizes compact assembly of end-effector. The Lagrange equation-based dynamic model of the mechanism is established, and the dynamic simulation demonstrated that the mechanism needs no torque in probe’s vertical position and larger torques are required when the probe moves towards the two ends. The proposed end-effector can be installed at the end of the robotic arm and provides a reference scheme for dexterously local operation with robot navigation in orthopedic ESWT.
目的 分析肌少症动物模型研究的现状、热点及发展趋势,为肌少症动物模型研究提供方向与基础资料.方法 检索 Web of Science(WOS)核心合集数据库中1900-01-01至2022-12-31的肌少症动物模型研究英文文献,以及中国知网(CNKI)数据库中 1915-2022 年的肌少症动物模型研究中文文献.应用文献计量分析软件VOSviewer分析发文量、发文国家/地区、机构、作者、期刊及关键词,以揭示该领域研究的主要国家和机构以及热点和前沿方向.结果 从WOS核心合集数据库共检索到肌少症动物模型相关文献2819篇,第1篇文献发表于1995年;美国是肌少症动物模型研究最多的国家,发文量为1105篇;发文机构最多的是美国佛罗里达大学,发文量为69篇;香港大学是我国发文量最多的机构,共发文20篇;美国学者Holly V R的发文量最多,发表50篇;肌少症动物模型研究刊文量最多的学术期刊是美国的FASEB J ournal,刊文量为196篇.CNKI数据库共检索到文献423篇,中文发文量最多的作者是李柱一,共发文19篇.WOS检索文献的关键词共现聚类分析发现,肌少症动物模型研究的热点可概括为肌少症与代谢相关性研究,肌少症动物模型细胞学及再生医学研究,肌少症动物模型与骨、肌肉和神经研究,以及肌少症与运动治疗研究.CNKI数据库检索发现失神经性肌少症模型研究最为广泛,中药对肌少症的作用研究也多有报告.文献阅读发现肌少症动物模型主要包括自然衰老模型、遗传修饰模型、高脂饮食诱导模型、失用性肌少症模型、激素诱导模型及其他疾病复合性的肌少症模型.结论 肌少症动物模型是近年来国内外研究的一个热点,文献计量分析在研究方向及热点、模式动物选择、动物模型制作、国内外交流与合作等方面可为肌少症动物模型研究提供基础.