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Abstract Background Wu et al. introduced a modified radiographic system that allows classification of all forms of CTD with excellent interobserver and intraobserver reliability. No study to date has evaluated the radiographic characteristics of Wu et al. type C3 CTD with osseous attachment at the level of the metacarpal. Objective This study aimed to evaluate the radiographic features of type C3 CTD according to the system of Wu et al., to describe the different anatomical subtypes of the duplication, and to propose a categorization approach to distinguish diverse surgical strategies based on the radiographic anatomy of this specific subtype of duplication. Methods We performed a retrospective analysis of 215 patients (221 thumbs) diagnosed with Wu et al. type C3 CTD at our Institution between 2015 and 2021. We evaluated all CTDs by examining the alignment of the interphalangeal (IP) and metacarpophalangeal (MP) joints and by assessing the presence of abnormal hypertrophic epiphysis of the primary thumb on posteroanterior (PA) radiographs. The proposed classification system has four types: Type I with good alignment of both MP and IP joints, Type II with ulnar deviation of the MP joint, Type III with radial deviation in the MP joint and Type IV with abnormal hypertrophic epiphysis of the distal phalanx of the main thumb with ulnar deviation of the IP joint with or without ulnar deviation of the MP joint. Results There were 140 male and 75 female patients with CTD (221 thumbs). There were 65 left, 144 right and 6 bilateral forms. The right-to-left, male-to-female and unilateral-to-bilateral ratios were 2.2:1, 1.9:1 and 35.8:1 respectively. The mean age at surgery was 22.3 ± 11.8 months (range, 8–80). The proposed classification system allowed the classification of all CTDs (n = 221). Specifically, 53 fingers were classified as Type I (24%), 136 as Type II (61.5%), 21 as Type III (9.5%), and 11 as Type IV (5%). Conclusion The proposed system is based on radiographic pathoanatomy and complements that of Wu et al. by identifying four distinct subtypes of deformity. It has the potential to improve inter-professional communication and guide surgery in patients with Wu et al. type C3 CTD. However, our results are preliminary and further research is needed to validate them. Level of evidence III.

Key Clinical Message Osteochondroma on the ventral scapula is clinically rare and can incur pseudo‐winged scapula and snapping syndrome if not treated. In this regard, surgical excision is suggested, if possible, with a minimally invasive approach to accelerate physical recovery. Abstract Osteochondroma is a common benign bone tumor, characterized by a cartilage‐capped osseous protuberance with cortical and medullary continuity with the underlying native bone. Osteochondroma is commonly found in the long bones, such as the proximal humerus, distal femur, and proximal tibia, but rarely seen in flat bones. We report a case of pedunculated osteochondroma on the ventral surface of left scapula in a young adult woman. She presented with a slight pseudo‐winged scapula, occasional pain, and snapping sound with motion of the left shoulder. The tumor was surgically resected using a minimally invasive approach, and an excellent outcome was obtained.

Abstract Background Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. Methods Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. Results From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. Conclusions Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.

Abstract Background Legg-Calvé-Perthes disease is a special self-limited disease in pediatric orthopedics with a high disability rate and a long-term course, and there is still no clear and effective therapeutic drug in clinic. This study aimed to investigate the potential efficacy of biochanin A, a kind of oxygen-methylated isoflavone compound, in treating Perthes disease based on network pharmacology, molecular docking and in vitro experiments. Methods IL-6 was used to stimulate human umbilical vein endothelial cells to construct endothelial cell dysfunction model. We demonstrated whether biochanin A could alleviate endothelial dysfunction through CCK8 assay, immunofluorescence. Targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. Targets of endothelial dysfunction were obtained from Genecards and OMIM databases. Protein–protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomics analyses were used to analyze the potential target and the key pathway of the anti-endothelial dysfunction activity of biochanin A. To validate the potential target-drug interactions, molecular docking and molecular dynamics simulations were performed and the result was proved by western blot. Results It was found that biochanin A can promote the expression of ZO-1, reduce the expression of ICAM-1, which means improving endothelial dysfunction. A total of 585 targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. A total of 10,832 targets of endothelial dysfunction were obtained from Genecards and OMIM databases. A total of 527 overlapping targets of endothelial dysfunction and biochanin A were obtained. AKT1, TNF-α, VCAM1, ICAM1, and NOS3 might be the key targets of the anti-endothelial dysfunction activity of biochanin A, and the key pathways might be PI3K-Akt and TNF signaling pathways. Molecular docking results indicated that the AKT1 and TNF-α had the highest affinity binding with biochanin A. Conclusion This study indicates that biochanin A can target AKT1 and TNF-α to alleviate endothelial dysfunction induced by IL-6 in Perthes disease, which provides a theoretical basis for the treatment of Perthes disease by using biochanin A.

In investigating the mechanical properties and chloride corrosion resistance of all-light shale ceramsite concrete (ALSCC), samples of ALSCC20–ALSCC45 with a compressive strength of C20–C45 were individually prepared. The compressive strength, split tensile strength, and elastic modulus of ALSCC were analyzed. Additionally, the chloride salt corrosion resistance of ALSCC was assessed by examining chloride ion penetration depth, steel corrosion rate, and compressive strength after ALSCC30 corrosion. Furthermore, the microstructure of ALSCC hydration products was observed using scanning electron microscopy (SEM). Results indicate that as the strength grade increases, the water–cement ratio decreases, and the internal structure becomes denser, thereby improving the mechanical and corrosion resistance properties of ALSCC. Notably, the chloride corrosion resistance of ALSCC surpasses that of ordinary concrete. SEM images reveal that the hydration of ceramsite with Ca(OH)2 in concrete generates Ca[Al(OH)4]2 precipitation and C–S–H gel, which enhances internal filling and improves chloride corrosion resistance. Furthermore, based on the results of the ALSCC30 corrosion test, a calculation model for predicting compressive strength in a chloride environment was proposed. This model effectively predicts the compressive strength of ALSCC under chloride exposure conditions.

Abstract Osteosarcoma (OS) is a primary bone tumor with high malignancy and the mechanism of hematogenous metastasis in OS is still not clear. The plasma exosomes derived from osteosarcoma play a key role in the process of tumor metastasis. Here, we established RNA-seq dataset for lncRNAs, circRNAs and mRNAs in plasma exosomes from 10 OS patients and 5 healthy donors. A total of 329.52 Gb of clean data was obtained. Besides, 1754 lincRNAs, 7096 known and 1935 new circRNA was identified. Finally, gene expression profiles and differentially expressed genes (DEGs) were analyzed among these 15 samples. There were 331 DEGs of mRNA, 132 of lincRNA and 489 of circRNA was obtained, respectively. This data set provides a significant resource for relevant researchers to excavate potential dysregulated lncRNAs, circRNAs and mRNAs of plasma exosomes in OS versus normal conditions.

Chemotherapy, a primary treatment for osteosarcoma (OS), has limited knowledge regarding its impact on tumor immune microenvironment (TIME). Here, tissues from 6 chemotherapy-naive OS patients underwent single-cell RNA sequencing (scRNA-seq) and were analyzed alongside public dataset (GSE152048) containing 7 post-chemotherapy OS tissues. CD45+ (PTPRC+) cells were used for cell clustering and annotation. Changes in immune cell composition pre- and post-chemotherapy were characterized. Totally, 28,636 high-quality CD45+ (PTPRC+) cells were extracted. Following chemotherapy, the proportions of regulatory T cells (Tregs) and activated CD8 T cells decreased, while CD8 effector T cells increased. GO analysis indicated that differentially expressed genes (DEGs) in T cells were associated with cell activation, adaptive immune response, and immune response to tumor cells. Furthermore, the proportions of plasma cells increased, while naive B cells decreased. B cell surface receptors expression was upregulated, and GO analysis revealed DEGs of B cells were mainly enriched in B cell-mediated immunity and B cell activation. Moreover, M2 polarization of macrophages was suppressed post-chemotherapy. Overall, this study elucidates chemotherapy remodels the OS TIME landscape, triggering immune heterogeneity and enhancing anti-tumor properties.

Abstract The study was aimed to determine the relationship between PLR (platelet to lymphocyte ratio) and the lateral pillar classification of Perthes disease, and to provide an alternative index for clinical diagnosis. In addition, the association of the PLR with the necrosis stage of Perthes disease was also explored. This was a retrospective study. 74 children with Perthes disease and 60 children in the healthy control group without femoral head necrosis in our hospital from 2012 to 2021 were collected. The general data and clinical parameters were collected from the hospital information system. The modified herring lateral pillar classification was collected for the fragmentation stage case group and the PLR, NLR (neutrophil to lymphocyte ratio), LMR (lymphocyte to monocyte ratio) and PNR (platelet to neutrophil ratio) were calculated. The cases were divided into four groups, herring A and B were group I, herring B/C and C were group II, the healthy control group was group III, and the necrosis stage was group IV. The hematological indexes (NLR, PLR, LMR, PNR) of children at different stages were statistically analyzed. Group I consisted of 36 patients, with an average age of 7.4 ± 2.0 years (3–11 years). Group II consisted of 23 patients, with an average age of 7.4 ± 1.9 years (4–12 years). Group III consisted of 60 patients, with a mean age of 7.4 ± 2.7 years (4–13 years). Group IV consisted of 15 patients, with an average age of 6.4 ± 1.7 years (3–10 years). The average values of PLR in groups I, II, III and IV were 131.98 ± 47.44, 122.19 ± 37.88, 102.46 ± 30.68 and 128.90 ± 28.11, respectively. It's worth noting that there was statistically significant difference among groups I, II and III (P = 0.003). The optimal threshold of PLR was 130.25, the sensitivity was 45.8% and the specificity was 85%. PLR was also significantly different between groups III and group IV. PLR was higher in Herring A and B classifications than in Herring B/C and C classifications. PLR had certain diagnostic value in both the necrosis stage and fragmentation stage as a risk factor.

This study used DC magnetron sputtering technology to fabricate Sm-Fe films and systematically investigated the phase transition behavior of Sm-Fe films with different Fe ratios. It was found that at higher Fe content, the films consisted of Sm2Fe17 or SmFe7 phases; as Fe content decreased, the films were mainly composed of SmFe3 or SmFe2 phases; at higher Sm content, the films primarily consisted of Sm phase. Sm is prone to volatilization at high temperatures, so Ta was used as a capping layer to effectively suppress Sm volatilization, successfully synthesizing pure SmFe2 phase films at a nearly 1:2 ratio. The magnetic properties and magnetostrictive behavior of the SmFe2 films were investigated, revealing that pure-phase SmFe2 films exhibit good perpendicular magnetic anisotropy and magnetostriction properties. The larger stress along the perpendicular-to-film direction, resulting from the absence of substrate-induced constraints, contributes to the excellent perpendicular magnetic anisotropy of the films. This study successfully synthesized pure-phase SmFe2 films and discovered a new method for fabricating perpendicularly anisotropic films. The research findings are of great significance for the efficient synthesis of desired films with high phase formation temperatures containing volatile elements.

Abstract The present study aimed to explore the influence of ulnar bow on the surgical treatment of Bado type I missed Monteggia fracture in children. A retrospective review of 28 patients was conducted between November 2010 and June 2020. All patients were treated with open reduction of the radial head and ulnar opening wedge osteotomy without annular ligament reconstruction. Four months (range 1–12 months) was the mean interval between injury onset and surgery. The average age of patients at the time of surgery was 6.1 years old (range 2–10 years old). The maximum ulnar bow (MUB) and MUB position (P-MUB) via radiography were evaluated. The patients were divided into two groups according to P-MUB, as follows: middle group (A) included 17 cases, and the MUB was located at 40–60% of the distal ulna; and distal group (B) included 11 cases, and the MUB was located at 20–40% from the distal end of the ulna. The mean follow-up period was 33 months (range 6–102 months). At the last follow-up, all the children showed stable reduction of the radial head, and the flexion function of elbow joint improved after the operation (P

BackgroundTumor infiltrating lymphocytes (TILs), the main component in the tumor microenvironment, play a critical role in the antitumor immune response. Few studies have developed a prognostic model based on TILs in osteosarcoma.MethodsScRNA-seq data was obtained from our previous research and bulk RNA transcriptome data was from TARGET database. WGCNA was used to obtain the immune-related gene modules. Subsequently, we applied LASSO regression analysis and SVM algorithm to construct a prognostic model based on TILs marker genes. What’s more, the prognostic model was verified by external datasets and experiment in vitro. ResultsEleven cell clusters and 2044 TILs marker genes were identified. WGCNA results showed that 545 TILs marker genes were the most strongly related with immune. Subsequently, a risk model including 5 genes was developed. We found that the survival rate was higher in the low-risk group and the risk model could be used as an independent prognostic factor. Meanwhile, high-risk patients had a lower abundance of immune cell infiltration and many immune checkpoint genes were highly expressed in the low-risk group. The prognostic model was also demonstrated to be a good predictive capacity in external datasets. The result of RT-qPCR indicated that these 5 genes have differential expression which accorded with the predicting outcomes.ConclusionsThis study developed a new molecular signature based on TILs marker genes, which is very effective in predicting OS prognosis and immunotherapy response.

The formation of osteoclasts and their hyperactive bone resorption are related to the aggregation of intracellular reactive oxygen species (ROS). Flavonoids, derived from plant active ingredients, can alleviate the symptoms of osteoporosis (OP). Isosinensetin (Iss) is a flavonoid with antioxidant effects obtained mainly from citrus fruits, and its effect on osteoclastogenesis has not been reported. In this study, we investigated the antioxidant activity of Iss on osteoclast differentiation and function, as well as the therapeutic impact of Iss on OP. We found that Iss inhibited osteoclastogenesis and suppressed the bone resorption function of osteoclasts. Additionally, Iss reduced receptor activator of nuclear factor-κB ligand (RANKL)-induced intracellular ROS. Using quantitative real-time polymerase chain reaction and western blot, we further found that Iss inhibited osteoclast-specific genes and related proteins, while promoting the expression of antioxidant enzyme-related genes and proteins. Mechanistically, Iss reduces intracellular ROS by activating nuclear factor-erythroid 2-related factor 2 (Nrf2) and its related antioxidant enzymes and inhibits the downstream nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways of ROS, which in turn inhibits nuclear factor of activated T cells 1 (NFATc1), and ultimately inhibits osteoclastogenesis. In vivo, by micro-computed tomography (Micro-CT) assay and histological analyses, we found that Iss could reduce bone loss in ovariectomized (OVX) mice. Therefore, Iss has the potential as an OP preventative and therapeutic drug option.

Abstract Aberrantly expressed lncRNAs have been reported to be closely related to the oncogenesis and development of osteosarcoma. However, the role of a dysregulated lncRNA-miRNA-mRNA network in osteosarcoma in the same individual needs to be further investigated. Whole transcriptome sequencing was performed on the tumour tissues and matched paratumour tissues of three patients with confirmed osteosarcoma. Two divergent lncRNA-miRNA-mRNA regulatory networks were constructed in accordance with their biological significance. The GO and KEGG analysis results of the mRNAs in the two networks revealed that the aberrantly expressed lncRNAs were involved in regulating bone growth and development, epithelial cell proliferation, cell cycle arrest and the N-terminal acetylation of proteins. The survival analysis results of the two networks showed that patients with high expression of GALNT3, FAM91A1, STC2 and SLC7A1 end in poorer prognosis. Likewise, patients with low expression of IGF2, BLCAP, ZBTB47, THRB, PKIA and MITF also had poor prognosis. A subnetwork was then constructed to demonstrate the key genes regulated by aberrantly expressed lncRNAs at the posttranscriptional level via the ceRNA network. Aberrantly expressed lncRNAs in osteosarcoma tissues regulate genes involved in cellular proliferation, differentiation, angiogenesis and the cell cycle via the ceRNA network.

Abstract Background At present, no predictive factor has been validated for the early efficacy of neoadjuvant chemotherapy (NACT) in osteosarcoma. The purpose of this study was to investigate the significance of the neutrophil-to-lymphocyte ratio (NLR) in predicting the response to NACT in extremity osteosarcoma. Methods Pathological complete response (pCR) was used to assess the efficacy of NACT. Receiver operating characteristic (ROC) curves and the Youden index (sensitivity + specificity-1) were used to determine the optimal cut-off values of the NLR. Univariate and multivariate analyses using logistic regression models were conducted to confirm the independent factors affecting the efficacy of NACT. Results The optimal NLR cut-off value was 2.36 (sensitivity, 80.0%; specificity, 71.3%). Univariate analysis revealed that patients with a smaller tumour volume, lower stage, lower NLR and lower PLR were more likely to achieve pCR. Multivariate analyses confirmed that the NLR before treatment was an independent risk factor for pCR. Compared to patients with a high NLR, those with a low NLR showed a more than 2-fold higher likelihood of achieving pCR (OR 2.82, 95% CI 1.36-5.17, p = 0.02). Conclusion The NLR is a novel and effective predictive factor for the response to NACT in extremity osteosarcoma patients. Patients with a higher NLR showed a lower percentage of pCR after NACT.

Abstract Background Ultrasound examination can be applied to the diagnosis of pediatric elbow fracture. This study aims to analyze the application value of ultrasound in the surgical treatment of supracondylar humeral fractures. Methods 64 children with supracondylar humeral fractures were treated with ultrasound-guided closed reduction and percutaneous pinning (CRPP), 31 patients were treated with CRPP under radiography guidence. The reduction effect of supracondylar humeral fractures was determined through the perioperative ultrasound images of the lateral, medial and posterior aspects of the elbow. Percutaneous pinning was performed after supracondylar humeral fractures were well reduced. A follow-up examination was performed and all the patients were evaluated according to Flynn’s criteria. Results The mean duration of surgery was 58.3 min (42–108 min) in the ultrasound group and 41.5 min (24-63 min) in the radiography group (P 0.05). After surgery, three patients had pin tract infection. One patient had ulnar nerve neurapraxia in the radiography group. No cases with Volkmann’s contracture were reported. Conclusion Ultrasound-guided CRPP is a safe and reliable surgical treatment of pediatric supracondylar humeral fractures. Trial registration Retrospectively registered.

Abstract The acetabular retroversion has a moderate incidence of 31–60% in all patients of the Perthes disease. It might be caused by posterior wall dysplasia based on recent animal researches. However, some studies support that hemipelvic retroversion is the main factor for the acetabular retroversion. The primary pathological factor of increasing retroversion angle is still controversial anatomically. This study aimed to identify whether there is acetabular retroversion in children with Perthes disease,and to find a method to distinguish version types. Forty children with unilateral Perthes disease who were admitted to our hospital from January 1, 2012 to December 31, 2018 were enrolled, and 40 controls were matched based on sex and age. The acetabular anteversion angle (AAA), internal wall anteversion angle (IWAA), anterior wall height of the acetabulum (A), acetabular posterior wall height (P), and acetabular width (W) were assessed on computed tomography (CT) at the level of the femoral head center. The acetabular wall difference index (AWDI; AWDI = P-A)/W*100) was calculated. The mean AAA was significantly lower in Perthes disease hips (10.59 (8.05–12.46)) than in contralateral hips (12.04 (9.02–13.33)) (p = 0.002) but did not differ from control hips (9.68 ± 3.76) (p = 0.465). The mean IWAA was significantly lower in Perthes hips (9.16 ± 3.89) than in contralateral hips (11.31 ± 4.04) (p = 0.000) but did not differ from control hips (9.43 ± 3.82) (p = 0.753). The mean AWDI did not differ between Perthes hips (0.41 ± 4.94) and contralateral hips (− 1.12 (− 4.50, 2.17)) (p = 0.06) or control hips (− 0.49 ± 5.46) (p = 0.437). The mean W was significantly higher in Perthes hips (44.61 ± 5.06) than in contralateral hips (43.36 ± 4.38) (p = 0.000) but did not differ from control hips (45.02 ± 5.01) (p = 0.719). The mean A and P did not differ between Perthes hips and contralateral hips or control hips. Correlation analysis of all hip joints revealed a significant correlation between AAAs and IWAAs (r = 0.772; r = 0.643; r = 0.608; and r = 0.540). Linear regression analysis revealed that AAAs increased with IWAAs. Multiple linear regression showed that IWAAs and AWDIs have good predictive value for AAAs in both Perthes and control hips (R2 = 0.842, R2 = 0.869). In patients with unilateral Perthes disease, the affected acetabulum is more retroverted than that on the contralateral side, which may be caused by hemipelvic retroversion. The measurements in this study could distinguish the form of acetabular retroversion. IWAAs and AWDIs can be used as new observations in future studies of acetabular version.

Osteoporosis is among the major contributors of pathologic fracture in postmenopausal women, which is caused by the bone metabolic disorder owing to the over-activation of osteoclasts. Inhibition of osteoclast differentiation and maturation has become a mainstream research interest in the prevention of osteoporosis. Isoliensinine (Iso) is a dibenzyl isoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-cancer activities. However, whether it can be used as a potential treatment for osteoporosis remains undiscovered. Here, we investigated whether Iso might suppress the differentiation of osteoclasts in vitro and in vivo to play an anti-osteoporosis role. Our results showed that Iso inhibits the formation of mature multinuclear osteoclasts induced by RANKL, the bone resorption, and the osteoclast-specific genes expression by blocking the nuclear translocation of NF-κB p65, and the effect was in a dosage-dependent way. Furthermore, we investigated the therapeutic effect of Iso on osteoporosis in ovariectomized (OVX) mice. We found that Iso attenuated bone loss in the OVX mice and significantly promoted BS, Conn. DN, Tb.Th, TB.N, and BV/TV Index. All in all, Iso showed a prominent effect of osteoclast inhibition, with great promise for treating osteoporosis.

Thick Nd-Fe-B permanent magnetic films with good perpendicular anisotropy have important applications in magnetic microelectromechanical systems (MEMSs). However, when the thickness of the Nd-Fe-B film reaches the micron level, the magnetic anisotropy and texture of NdFeB film will become worse, and it is also prone to peeling during heat treatment, which seriously limits their applications. In this paper, Si(100)/Ta(100 nm)/NdxFe91−xB9(x = 14.5, 16.4, 18.2)/Ta (100 nm) films with thicknesses of 2–10 μm are prepared by magnetron sputtering. It is found that gradient annealing (GN) could help improve the magnetic anisotropy and texture of the micron-thickness film. When the Nd-Fe-B film thickness increases from 2 μm to 9 μm, its magnetic anisotropy and texture do not deteriorate. For the 9 μm Nd-Fe-B film, a high coercivity of 20.26 kOe and high magnetic anisotropy (remanence ratio Mr/Ms = 0.91) are achieved. An in-depth analysis of the elemental composition of the film along the thickness direction is conducted, and the presence of Nd aggregation layers at the interface between the Nd-Fe-B and the Ta layers is confirmed. The influence of thicknesses of the Ta buffer layer on the peeling of Nd-Fe-B micron-thickness films after high-temperature annealing is investigated, and it is found that increasing the thickness of the Ta buffer layer could effectively inhibit the peeling of Nd-Fe-B films. Our finding provides an effective way to modify the heat treatment peeling of Nd-Fe-B films. Our results are important for the development of Nd-Fe-B micron-scale films with high perpendicular anisotropy for applications in magnetic MEMS.

Abstract Background To investigate the clinical imaging manifestations, diagnosis and treatment of intraperitoneal extraosseous osteosarcoma. Case presentation A 52-year-old male patient with intraperitoneal extraosseous osteosarcoma was retrospectively analyzed. He suffered from left lower abdominal pain accompanied by mass for 6 months. On abdominal CT scan, multiple patchy and banded calcification were found. The largest is about six centimeters in diameter and underwent mass resection. Postoperative pathology revealed retroperitoneal osteosarcoma. The reported intraperitoneal extraosseous osteosarcoma was analyzed and the related literature was reviewed. Two years after operation, the patients had recurrence of the tumors and invaded sigmoid colon, peritoneum and bladder. Palliative operation was performed to remove the tumors in the bladder and transverse colostomy was performed. The patients were followed up by telephone and died 2 months after the second operation. Conclusions Intraperitoneal extraosseous osteosarcoma has a low incidence and has no specific imaging features. Surgical resection is the main treatment and the prognosis is poor.

Abstract Background Primary synovial chondromatosis is a rare benign disease that occurs in the joint mucosa. Case presentation In this case report, a 14-year-old gymnast sustained pain in both elbows for 2 months with limited elbow joint activity. The initial diagnosis of bilateral elbow synovial chondromatosis was performed by physical examination and imaging report. Later, the patient was treated with open surgery on both sides of the elbow, including all loose bodies were removed out and the proliferative synovia were cut off. Histopathology reports confirmed synovial chondromatosis. Conclusions The report introduced a case about synovial chondromatosis in bilateral elbow found in a 14-year-old girl, which is rarely involved in bilateral elbow and rarely found in adolescents. This case report aims to provide a treatment option for surgeons in similar situations.

Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

Icarisid II, one of the main active components of Herba Epimedii extracts, shows potent antitumor activity in various cancer cell lines, including osteosarcoma cells. However, the anticancer mechanism of icarisid II against osteosarcoma U2OS needs further exploration. This study aims to investigate further antitumor effects of icarisid II on human osteosarcoma cells and elucidate the underlying mechanism. We cultivated human osteosarcoma USO2 cells in vitro using different concentrations of icarisid II (0–30 µM). Cell viability was detected at 24, 48, and 72 h using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis. Cell cycle was tested by flow cytometry after treatment with icarisid II for 48 h. Annexin V–allophycocyanin and 7-aminoactinomycin D staining were conducted to detect cell apoptosis. Quantitative real-time polymerase chain reaction and Western blot assay were performed to measure the levels of genes and proteins related to cell cycle and apoptosis. Results showed that icarisid II significantly inhibited the proliferation and induced apoptosis of human osteosarcoma U2OS cells. The half maximal inhibitory concentration values were 14.44, 11.02, and 7.37 µM at 24, 48, and 72 h, respectively. Cell cycle was arrested in the G2/M phase in vitro. In addition, icarisid II upregulated the expression levels of P21 and CyclinB1 whereas downregulated the expression levels of CyclinD1, CDC2, and P-Cdc25C, which were related to cell cycle arrest in U2OS cells. The cell apoptotic rate increased in a dose-dependent manner after treatment with icarisid II for 48 h. Icarisid II induced apoptosis by upregulating Bax, downregulating Bcl-2, and activating apoptosis-related proteins, including cleaved caspase-3, caspase-7, caspase-9, and poly (ADP-ribose) polymerase. These data indicate that icarisid II exhibits an antiproliferation effect on human osteosarcoma cells and induces apoptosis by activating the caspase family in a time- and dose-dependent manner in vitro. Therefore, icarisid II may be used as a candidate agent for the clinical treatment of osteosarcoma in the future.

Background: Tumor infiltrating lymphocytes (TILs), the main component in the tumor microenvironment, play a critical role in the antitumor immune response. Few studies have developed a prognostic model based on TILs in osteosarcoma. Methods: ScRNA-seq data was obtained from our previous research and bulk RNA transcriptome data was from TARGET database. WGCNA was used to obtain the immune-related gene modules. Subsequently, we applied LASSO regression analysis and SVM algorithm to construct a prognostic model based on TILs marker genes. What's more, the prognostic model was verified by external datasets and experiment in vitro. Results: Eleven cell clusters and 2044 TILs marker genes were identified. WGCNA results showed that 545 TILs marker genes were the most strongly related with immune. Subsequently, a risk model including 5 genes was developed. We found that the survival rate was higher in the low-risk group and the risk model could be used as an independent prognostic factor. Meanwhile, high-risk patients had a lower abundance of immune cell infiltration and many immune checkpoint genes were highly expressed in the low-risk group. The prognostic model was also demonstrated to be a good predictive capacity in external datasets. The result of RT-qPCR indicated that these 5 genes have differential expression which accorded with the predicting outcomes. Conclusions: This study developed a new molecular signature based on TILs marker genes, which is very effective in predicting OS prognosis and immunotherapy response. [ABSTRACT FROM AUTHOR]