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Background Due to its occult position, complex anatomical structure, and spatial relationships, the causative tumor of Tumor-Induced Osteomalacia (TIO) in the hip region is quite difficult to detect and qualitatively diagnose in clinical practice. In this regard, clinicians often lack sufficient knowledge about such tumors, leading to frequent missed diagnoses, misdiagnoses, and unreasonable treatment. Objective This study aimed to investigate the clinical characteristics of TIO patients with culprit soft tissue tumors in the hip region and evaluate the effect of surgical treatment on these individuals to improve clinicians’ understanding of the rare phenomenon. Methods The clinical data of all patients, from January 2013 to January 2023, who underwent surgical treatment for hip located culprit soft tissue tumors by the subspecialty group on bone and soft tissue tumors at our institution, were retrospectively analysed. Specifically, the clinical characteristics and therapeutic effects were examined and the patients’ clinical experience was summarized. Results Twenty-two patients, who met the inclusion criteria, were included. All patients experienced varying degrees of bone pain, commonly accompanied by weakness (16/22) and limited mobility (21/22), and 10 patients (45.5%) experienced a significant reduction in body height during the course of the disease. All patients underwent orthopedic surgery in the hip region, as hypophosphatemia occurred in all of them. Pathological diagnosis was confirmed to be consistent with causative tumors of TIO. All patients experienced a gradual increase in serum phosphorus postoperatively during short-term follow-up. The follow-up period was between 1 and 10 years, and the postoperative serum phosphorus levels were monitored at our hospital or other facilities close to the patients. Conclusions Oncogenic soft tissue tumors for TIO in the hip region are occult, making clinical misdiagnoses or missed diagnoses highly likely. Therefore, enhancing the clinician’s understanding of this rare condition is imperative. Notably, for TIO patient whose culprit tumor can be located, complete surgical resection of the causative tumor is the best treatment option. Furthermore, close postoperative monitoring of serum phosphorus is necessary, and patients should be subjected to long-term follow-up for prompt detection of recurrent conditions. Highlights Tumor-induced osteomalacia caused by causative soft tissue tumor in the hip region is a rare entity, resulting in great challenges to orthopedists. Qualitative and localized diagnosis led by multi-disciplinary team is a prerequisite for subsequent surgical intervention. For the inguinally located culprit tumors, it may be quite effective after remove the culprit tumor directly and surgical resection may bring huge benefit. Exploring the site of onset of the causative tumor is beneficial for improving the treatment strategy of orthopedic surgery and understanding the prognostic characteristics of TIO patients.

Background: With the intensification of population aging, osteoporosis has become one of the significant public health issues affecting human health. Currently available medications for treating osteoporosis are associated with various adverse effects and resistance issues. Oligonucleotide drugs show great potential. Effective delivery systems are essential to enhance the stability, bioavailability, and targeting of sRNA drugs. Lipid nanoparticles (LNPs) show promise as alternative osteoporosis therapeutics. This study explores the potential of LNPs as an effective delivery system to treat osteoporosis. Methods: LNPs were prepared using microfluidic techniques with varying lipid compositions, and characterized in terms of size, zeta potential, and entrapment efficiency (EE%). Dynamic light scattering (DLS) was employed to determine the size of the LNPs. The zeta potential was measured using electrophoretic light scattering. The pharmacodynamic effects and safety were then evaluated in a mouse model through intravenous administration. Results: Several lipid nanoparticle (LNP) formulations with different nitrogen/phosphorus ratios and different DMG-PEG2000 ratios were examined, and a lead candidate that supports delivery of sRNA in animal models of osteoporosis was identified. In OVX mice, LNP-sRNA significantly improved bone mineral density (BMD), trabecular microstructure, and biomechanical strength. Safety assessments revealed no systemic toxicity. It is shown that the optimized LNPs can serve as a promising delivery system to mediate sRNA delivery to bone tissue. Conclusions: After comparison of in vitro and in vivo properties, the optimized LNPs demonstrated good comprehensive performance as a delivery system for osteoporosis treatment. These results highlight the potential of the optimized LNPs as an ideal delivery system for osteoporosis, offering improved therapeutic efficacy and reduced systemic side effects.

Brain metastasis is the most commonly seen brain malignancy, frequently originating from lung cancer, breast cancer, and melanoma. Brain tumor has its unique cell types, anatomical structures, metabolic constraints, and immune environment, which namely the tumor microenvironment (TME). It has been discovered that the tumor microenvironment can regulate the progression, metastasis of primary tumors, and response to the treatment through the particular cellular and non-cellular components. Brain metastasis tumor cells that penetrate the brain–blood barrier and blood–cerebrospinal fluid barrier to alter the function of cell junctions would lead to different tumor microenvironments. Emerging evidence implies that these tumor microenvironment components would be involved in mechanisms of immune activation, tumor hypoxia, antiangiogenesis, etc. Researchers have applied various therapeutic strategies to inhibit brain metastasis, such as the combination of brain radiotherapy, immune checkpoint inhibitors, and monoclonal antibodies. Unfortunately, they hardly access effective treatment. Meanwhile, most clinical trials of target therapy patients with brain metastasis are always excluded. In this review, we summarized the clinical treatment of brain metastasis in recent years, as well as their influence and mechanisms underlying the differences between the composition of tumor microenvironments in the primary tumor and brain metastasis. We also look forward into the feasibility and superiority of tumor microenvironment-targeted therapies in the future, which may help to improve the strategy of brain metastasis treatment.

Augmented reality (AR) technology is gradually being applied in surgical teaching as an innovative teaching method. Developing innovative teaching methods to replicate clinical theory and practical teaching scenarios, simulate preoperative planning and training for bone tumor surgery, and offer enhanced training opportunities for young physicians to acquire and apply clinical knowledge is a crucial concern that impacts the advancement of the discipline and the educational standards for young orthopedic physicians. This study explores the application effect of augmented reality technology in anatomy teaching and surgical clinical teaching for spinal tumor. The method utilizes virtual reality and augmented reality technology to present a spinal tumor model and the surgical process of percutaneous vertebroplasty. We conducted a random selection of 12 students forming into the augmented reality teaching group and 13 students forming into the traditional teaching group among the 8-year medical students from Peking Union Medical College and Tsinghua University, ensuring that the age and learning stage of the students in both groups were similar. Two groups of students were taught using traditional teaching methods and augmented reality technology-assisted teaching methods, respectively. A questionnaire survey was conducted after class to assess the quality of course instruction, student motivation in learning, their proficiency in anatomical structures, their comprehension of spinal tumor growth and metastasis, and their understanding and proficiency in percutaneous vertebroplasty. This study was the first to apply augmented reality technology in teaching, using spinal tumors and percutaneous vertebroplasty as examples, a head-mounted augmented reality device was used to create learning scenarios, presenting the complex three-dimensional spatial structure intuitively. The two groups of students differ significantly in their rating of teaching quality, enthusiasm for learning, knowledge of anatomical features, understanding of spinal trabecular structure, and understanding of steps in percutaneous vertebroplasty. The augmented reality technology-assisted teaching system demonstrates outstanding advantages. Augmented reality technology has great potential and broad prospects in teaching bone tumors, which can help improve the visualization, interactivity, and three-dimensional spatial sense of medical teaching in spinal tumor. The application and development prospects of using augmented reality technology for anatomy instruction, surgical teaching, and simulation training are extensive.

Objective The orthopedic surgical treatment strategies for patients with tumor‐induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in‐depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor‐induced osteomalacia (TIO), whose causative tumors are located in the hip bones. Methods A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub‐professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery‐related data, perioperative changes in blood phosphorus levels, and postoperative follow‐up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non‐normally distributed data are shown as the means and 25th and 75th interquartile ranges. Results The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. Conclusion In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis. The location of the causative tumor in the hip bone is hidden and diverse, resulting in great challenges to endocrinologists and orthopedists. For the intraosseous tumor in hip bone, it may be quite difficult to remove the culprit tumor. In this situation, the proportion of recurrent/refractory cases has significantly increased, posing a huge challenge to the diagnosis and treatment of patients with this type of disease.

ObjectivesThis study aimed to evaluate the value of nodal grouping (NG), defined as the presence of at least three contiguous lymph nodes (LNs) within one LN region, in staging and management of patients with non-metastatic nasopharyngeal carcinoma (NPC).MethodsMR images were reviewed to evaluate LN variables, including NG. The Kaplan–Meier method and multivariate Cox regression models evaluated the association between the variables and survival. Harrell’s concordance index (C-index) was used to measure the performance of prognostic models. The outcome of induction chemotherapy (IC) in patients with and without NG was compared using matched-pair analysis.ResultsIn 1224 patients enrolled, NG was found to be an independent prognostic factor for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and regional recurrence-free survival. The hazard ratio and 95% confidence interval (CI) of NG for OS (3.86, 2.09–7.12) were higher than those of stage N2 (3.54, 1.89–6.70). On upgrading patients with NG from stages N1 to N2, the revised N staging yielded a higher C-index compared to the American Joint Committee on Cancer system in predicting PFS (0.664 vs. 0.658, p = 0.022) and DMFS (0.699 vs. 0.690, p = 0.005). Results of the matched-pair analysis revealed that for patients with NG in stages N1 and N2, IC was correlated with improved OS (p = 0.022), PFS (p = 0.007), and DMFS (p = 0.021).ConclusionsNG is a significant prognostic factor for patients with NPC. Patients with NG may be upgraded from stages N1 to N2. NG was also a marker for identifying patients who would benefit from IC.Key Points• Nodal grouping, defined as the presence of at least three contiguous LNs within one LN region on MRI, was identified as a significant prognostic factor.• In patients with nasopharyngeal carcinoma, nodal grouping may influence lymph node staging.• Nodal grouping was a marker for identifying patients who may benefit from induction chemotherapy.

Non-Hermitian quantum systems exhibit many novel physical properties of quantum states. We consider a non-Hermtian graphene model based on the tight-binding approximation with the coupling of the graphene and the substrate. We analyze the complex energy structure of this model and its exceptional points as well as relevant topological invariants. We give the analytic complex Berry connection and Berry curvature in the Brillouin zone and investigate numerically the relationships between the complex Berry curvature and the complex energy band structures. We find that the behaviors of the complex Berry curvature depend on the complex energy band structures. The occurrence of the peaks of both real and imaginary parts of the complex Berry curvature corresponds to the exceptional (gapless) points in the Brillouin zone. In particular, the Dirac cone of the imaginary part of the Berry curvature occurs and corresponding to the occurrence of the flat real energy band for the non-Hermitian parameter η = 3 . These results provide some novel insights to the relationship between the non-Hermitian graphene, geometry, and topological invariants.

The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8 +  cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.

Non-Hermitian systems as theoretical models of open or dissipative systems exhibit rich novel physical properties and fundamental issues in condensed matter physics. We propose a generalized local–global correspondence between the pseudo-boundary states in the complex energy plane and topological invariants of quantum states. We find that the patterns of the pseudo-boundary states in the complex energy plane mapped to the Brillouin zone are topological invariants against the parameter deformation. We demonstrate this approach by the non-Hermitian Chern insulator model. We give the consistent topological phases obtained from the Chern number and vorticity. We also find some novel topological invariants embedded in the topological phases of the Chern insulator model, which enrich the phase diagram of the non-Hermitian Chern insulators model beyond that predicted by the Chern number and vorticity. We also propose a generalized vorticity and its flipping index to understand physics behind this novel local–global correspondence and discuss the relationships between the local–global correspondence and the Chern number as well as the transformation between the Brillouin zone and the complex energy plane. These novel approaches provide insights to how topological invariants may be obtained from local information as well as the global property of quantum states, which is expected to be applicable in more generic non-Hermitian systems.

Objective To undertake a systematic review and meta-analysis to evaluate the prognostic value of Forkhead box F2 (FOXF2) levels in different types of cancers prone to bone metastasis. Methods A systematic search of publications listed in electronic databases (The Web of Science, EMBASE®, PubMed®, PMC, Science Direct and CNKI) from inception to 5 November 2020 was conducted. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the relationship between FOXF2 levels and patient prognosis including overall survival (OS) and disease-free survival (DFS). Results Sixteen studies enrolling 8461 participants were included in the meta-analysis. High levels of FOXF2 were a predictor of OS (HR: 0.66; 95% CI 0.51, 0.86) and DFS (HR: 0.60; 95% CI 0.48, 0.76). The trim-and-fill analysis, sensitivity analysis and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Conclusion These current findings indicate that high FOXF2 levels could be an indicator of a good prognosis in cancer patients with tumours that are prone to bone metastasis. FOXF2 levels might be a clinically important prognostic biomarker.