Search

PurposeTo examine clinical outcomes of a specialized modular prosthesis used to fill a bone deficiency following removal of femoral shaft metastases.MethodsEighteen patients with femoral shaft metastases who underwent en bloc resection and implantation of a personalized modular prosthesis between December 2014 and December 2019 were retrospectively analyzed. Pain, limb function, and quality of life were evaluated using the visual analog scale (VAS), Musculoskeletal Tumor Society (MSTS) scale, International Society of Limb Salvage (ISOLS) scoring system, Karnofsky Performance Status (KPS) scale, and Nottingham Health Profile (NHP) scale. The Kaplan–Meier technique was used to analyze patient survival.ResultsThe operation duration was 90–150 min (mean, 115 min), and the osteotomy length was 9–16 cm (mean, 11.72 cm). The patients were followed for 12–62 months (mean, 25.28 months). The VAS and NHP ratings were lower at 3, 6, and 12 months after surgery than before surgery, while the MSTS, ISOLS, and KPS scores were higher after surgery than they had been before. These differences were statistically significant (PConclusionEn bloc excision and implantation of a personalized modular prosthesis can reduce pain and improve the ability of patients with femoral shaft metastases to perform daily activities, thereby improving their quality of life.

Exosomes as nanosized membrane vesicles, could targeted deliver therapeutic agents by modification with target ligands. Exosome-derived non-coding RNAs play a vital role in the development of tumors. Previous evidences reveal that long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) has anti-tumor properties. Whereas, the inhibitory effects of exosome-derived lncRNA MEG3 in osteosarcoma (OS) remain largely unknown. In this study, we utilize the engineering technology to combine exosome and lncRNA for tumor-targeting therapy of OS. We elucidated the anti-OS effects of lncRNA MEG3, and then prepared the c(RGDyK)-modified and MEG3-loaded exosomes (cRGD-Exo-MEG3). The engineered exosomes cRGD-Exo-MEG3 could deliver more efficiently to OS cells both in vitro and in vivo. In this way, cRGD-Exo-MEG3 facilitate the anti-OS effects of MEG3 significantly, with the help of enhanced tumor-targeting therapy. This study elucidates that engineered exosomes as targeted lncRNA MEG3 delivery vehicles have potentially therapeutic effects for OS.

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient’s show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

Osteosarcoma (OS) is the most common primary malignancy of bone. Epigenetic regulation plays a pivotal role in cancer development in various aspects, including immune response. In this study, we studied the potential association of alterations in the DNA methylation and transcription of immune-related genes with changes in the tumor microenvironment (TME) and tumor prognosis of OS. We obtained multi-omics data for OS patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. By referring to curated immune signatures and using a consensus clustering method, we categorized patients based on immune-related DNA methylation patterns (IMPs), and evaluated prognosis and TME characteristics of the resulting patient subgroups. Subsequently, we used a machine-learning approach to construct an IMP-associated prognostic risk model incorporating the expression of a six-gene signature (MYC, COL13A1, UHRF2, MT1A, ACTB, and GBP1), which was then validated in an independent patient cohort. Furthermore, we evaluated TME patterns, transcriptional variation in biological pathways, somatic copy number alteration, anticancer drug sensitivity, and potential responsiveness to immune checkpoint inhibitor therapy with regard to our IMP-associated signature scoring model. By integrative IMP and transcriptomic analysis, we uncovered distinct prognosis and TME patterns in OS. Finally, we constructed a classifying model, which may aid in prognosis prediction and provide a potential rationale for targeted- and immune checkpoint inhibitor therapy in OS.

Background Osteosarcoma is a malignant bone tumor that usually affects adolescents aged 15–19 y. The DNA damage response (DDR) is significantly enhanced in osteosarcoma, impairing the effect of systemic chemotherapy. Targeting the DDR process was considered a feasible strategy benefitting osteosarcoma patients. However, the clinical application of DDR inhibitors is not impressive because of their side effects. Chinese herbal medicines with high anti-tumor effects and low toxicity in the human body have gradually gained attention. 2-Hydroxy-3-methylanthraquinone (HMA), a Chinese medicine monomer found in the extract of Oldenlandia diffusa, exerts significant inhibitory effects on various tumors. However, its anti-osteosarcoma effects and defined molecular mechanisms have not been reported. Methods After HMA treatment, the proliferation and metastasis capacity of osteosarcoma cells was detected by CCK-8, colony formation, transwell assays and Annexin V-fluorescein isothiocyanate/propidium iodide staining. RNA-sequence, plasmid infection, RNA interference, Western blotting and immunofluorescence assay were used to investigate the molecular mechanism and effects of HMA inhibiting osteosarcoma. Rescue assay and CHIP assay was used to further verified the relationship between MYC, CHK1 and RAD51. Results HMA regulate MYC to inhibit osteosarcoma proliferation and DNA damage repair through PI3K/AKT signaling pathway. The results of RNA-seq, IHC, Western boltting etc. showed relationship between MYC, CHK1 and RAD51. Rescue assay and CHIP assay further verified HMA can impair homologous recombination repair through the MYC-CHK1-RAD51 pathway. Conclusion HMA significantly inhibits osteosarcoma proliferation and homologous recombination repair through the MYC-CHK1-RAD51 pathway, which is mediated by the PI3K-AKT signaling pathway. This study investigated the exact mechanism of the anti-osteosarcoma effect of HMA and provided a potential feasible strategy for the clinical treatment of human osteosarcoma. Graphical Abstract

Background Accumulated evidence indicates that cholesterol is offensive to bone metabolism. Therefore, we examined the real-world study among total cholesterol and total bone mineral density (BMD). We investigated the relationship between total cholesterol and total BMD among 10,039 US participants aged 20–59 years old over the period 2011–2018 from the NHANES. Methods To analyze the relationship among total cholesterol and total BMD, multivariate linear regression models were used. Fitted smoothing curves, generalized additive models, and threshold effect analysis were also conducted. Results After adjusting for additional covariates, weighted multivariable linear regression models indicated total cholesterol concentration levels exhibited a negative relationship with total BMD, particularly among participants aged 20–29 years. Concerning subgroup analysis, stratified by gender, race/ethnicity and age group, the negative correlation of total cholesterol with total BMD dwelled in both female and male as well as in whites and other races (including Hispanic and Multi-Racial), but not in non-Hispanic blacks and Mexican American. In other races, this relationship presented a nonlinear association (inflection point: 6.7 mmol/L) with a U-shaped curve. Among participants aged 40 to 49 years, this relationship also followed a nonlinear association (inflection point: 5.84 mmol/L), indicating a saturation effect. Moreover, the three types of diabetes status were found to have negative, U-shaped, and positive relationships. In participants with borderline diabetes status, the relationship of total cholesterol with total BMD was a U-shaped curve (inflection point: 4.65 mmol/L). Conclusions For US young adults (20–29 years old), our study revealed a negative relationship between total cholesterol and total BMD. This association followed a U-shaped curve (inflection point: 4.65 mmol/L) in borderline diabetes status participants, a saturation curve (inflection point: 5.84 mmol/L) in participants aged 40–49 years and a nonlinear curve (inflection point: 6.7 mmol/L) in other races (including Hispanic and Multi-Racial). Therefore, keeping total cholesterol concentration at a reasonable level for young adults and diabetic population might be an approach to prevent osteoporosis or osteopenia.

To investigate the method of reconstruction of the sacroiliac joint in patients who underwent benign tumour curettage and analyse the effect of internal fixation with lumbo-iliac screws and connecting rod insertion after filling the defect with bone cement.Twenty-four patients with benign sacroiliac joint tumours underwent curettage and filling of the defect with bone cement, followed by lumbo-iliac screw and connecting rod insertion. The visual analogue scale (VAS) was used to assess pain, and the Musculoskeletal Tumour Society (MSTS) score was used to assess hip function.All patients were followed-up for 24-96 months (average, 42.2 months). The postoperative VAS score was significantly lower than the preoperative score (p 0.05), while the postoperative MSTS score was significantly higher than the preoperative score (p 0.05). One patient had delayed healing of the surgical incision; no complications occurred in the remaining patients.For benign sacroiliac joint tumours, the combination of filling of defects with bone cement and internal lumbo-iliac fixation can relieve pain quickly, and achieve good limb function.

Disruption of the intervertebral disc extracellular matrix (ECM) is a hallmark of intervertebral disc degeneration (IDD), which is largely attributed to excessive oxidative stress. However, there is a lack of clinically feasible approaches to promote the reconstruction of the disc ECM. Glucagon-like peptide-1 (GLP-1), a safe polypeptide hormone adopted to treat type 2 diabetes mellitus, has shown great potential for relieving oxidative stress-related damage. To our knowledge, this is the first study to reveal that exenatide, a GLP-1 receptor (GLP-1R) agonist, can upregulate disc ECM synthesis and attenuate oxidative stress-induced ECM degradation and IDD. Mechanistically, we found that exenatide inhibited the activation of mitogen-activated protein kinases (MAPK) signaling pathway and the formation of BATF/JUNs heterodimers (an index of activator protein-1 (AP-1) activity). The restoration of MAPK signaling activation reversed the protective effects of exenatide and enhanced downstream BATF/JUNs binding. BATF overexpression was also found to aggravate disc ECM damage, even in the presence of exenatide. In summary, exenatide is an effective agent that regulates ECM anabolic balance and restores disc degeneration by inhibiting MAPK activation and its downstream AP-1 activity. The present study provides a therapeutic rationale for activating the GLP-1 receptor against IDD and establishes the important role of AP-1 activity in the pathogenesis of IDD.

Osteosarcoma is a rare malignant bone-originating tumor that usually occurs in young people. Programmed cell death 1 ligand 1 (PD-L1), an immune checkpoint protein, is highly expressed in osteosarcoma tissues. Several recent studies have indicated that the tumor-related role of PD-L1 in tumors, especially non-plasma membrane (NPM)-localized PD-L1, is not limited to immune regulation in osteosarcoma. Here, mass spectrometry analysis is combined with RNA-seq examination to identify the intracellular binding partners of PD-L1 and elucidate the underlying mechanism of its action. It is found that the NPM-localized PD-L1 interacted with Insulin-like growth factor binding protein-3 (IGFBP3) to promote osteosarcoma tumor growth by activating mTOR signaling. This interaction is enforced after phosphoglyceratekinase1 (PGK1)-mediated PD-L1 phosphorylation. Based on these findings, a phosphorylation-mimicking peptide is designed from PD-L1 and it is encapsulated with a Cyclic RGD (cRGD)-modified red blood cell membrane (RBCM) vesicle (Peptide@cRGD-M). The Peptide@cRGD-M precisely delivers the PD-L1-derived phosphorylation-mimicking peptide into osteosarcoma lesions and significantly promotes its therapeutic effect on the tumor. Therefore, this investigation not only highlights the function of NPM-localized PD-L1, but also uses an engineering approach to synthesize a small molecular peptide capable of inhibiting osteosarcoma growth.

To investigate the mid-term effectiveness of three-dimensional (3D) printed osteotomy guide plate and personalized prosthesis in knee-preserving tumor resection.The clinical data of 12 patients who underwent knee-preserving tumor resection and reconstruction with 3D printed osteotomy guide plate and personalized prosthesis between September 2016 and October 2018 were retrospectively analyzed. There were 7 males and 5 females. The age ranged from 7 to 59 years, with a median of 44.5 years. There were 11 cases of osteosarcoma and 1 case of fibrosarcoma, all of which were Enneking grade ⅡB. The distance from the tumor to the joint surface was 5.5-8.2 cm, with an average of 6.94 cm. Incision healing, tumor recurrence, periprosthetic fracture, and aseptic loosening were observed after operation. The Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate the function of the patients, and the knee flexion range of motion was measured.The 12 patients were followed up 41-66 months, with an average of 54.5 months. The length of osteotomy ranged from 14 to 26 cm, with an average of 22.08 cm. Except for 2 patients with superficial infection of incision tissue, no deep infection involving the prosthesis occurred, no patient underwent revision surgery because of prosthesis infection. During the follow-up, local recurrence occurred in 2 cases and distant metastasis occurred in 3 cases. The overall disease-free survival rate was 58.3%. Two patients died of lung metastasis, and the overall survival rate was 83.3%. One patient underwent amputation due to local recurrence, and 1 patient underwent total knee arthroplasty due to prosthesis rupture. No aseptic loosening of the prosthesis and periprosthetic fracture occurred during the follow-up, and the overall prosthesis survival rate was 83.3%. At last follow-up, 10 patients obtained satisfactory knee flexion range of motion that ranged from 95° to 125°, with an average of 110°. Two children could not cooperate with early rehabilitation treatment due to pain, and the knee flexion range of motion was not ideal (50°, 75°). All patients achieved acceptable lower limb function with MSTS scores ranged from 26 to 30, with an average of 28. All patients walked without crutches.The treatment of malignant bone tumors around the knee joint with 3D printed osteotomy guide plate and personalized prosthesis can preserve the articular surface, obtain good limb function, reduce the risk of aseptic loosening of prosthesis, and achieve better mid-term effectiveness.探讨在膝关节周围恶性骨肿瘤患者中使用3D打印截骨导板与个性化假体进行保膝治疗的中期疗效。.回顾分析2016年9月—2018年10月采用3D打印截骨导板与个性化假体进行保留关节面的肿瘤切除重建术治疗的12例膝关节周围恶性肿瘤患者临床资料。其中男7例，女5例；发病年龄7～59岁，中位年龄44.5岁。骨肉瘤11例、纤维肉瘤1例，均为Enneking ⅡB期。肿瘤与关节面距离为5.5～8.2 cm，平均6.94 cm。术后观察患者切口愈合、肿瘤复发、有无假体周围骨折及无菌性松动等情况，使用美国肌肉骨骼肿瘤学会（MSTS）评分进行功能评价，并测定膝关节屈曲活动度。.12例患者均获随访，随访时间41～66个月，平均54.5个月。截骨长度为14～26 cm，平均22.08 cm。除2例患者出现切口浅表感染，未发生累及假体的深部感染，无患者因假体感染行翻修手术。随访期间2例发生局部复发，3例发生远处转移，患者总无病生存率为58.3%。2例患者因肺转移死亡，患者总生存率为83.3%。1例患者因局部复发截肢，1例假体断裂行人工全膝关节置换术翻修；随访期间未发生假体无菌性松动及假体周围骨折，总假体生存率为83.3%。末次随访时10例患者获得了满意膝关节屈曲活动度，达95°～125°，平均110°；2例患儿因疼痛无法配合早期康复治疗，膝关节屈曲活动度恢复不理想，分别为50° 和75°。所有患者均获得了可接受的下肢功能，MSTS评分为26～30分，平均28分；患者均可不拄拐独立行走。.3D打印截骨导板与个性化假体治疗膝关节周围恶性骨肿瘤，可以保留关节面，患者可获得良好肢体功能，减少假体无菌性松动风险，中期疗效较好。.

We present a rare case of a primary intradural extramedullary Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) in the thoracolumbar spine and review the current literature. We describe the imaging manifestations, pathological features, surgical methods, and patient survival to shed light on the clinical management of this rare tumor. A 32-year-old man experienced progressive low back pain for more than 1 month. An intradural extramedullary tumor from T12 to L2 was detected on magnetic resonance imaging. He underwent a thoracolumbar laminotomy for decompression, complete excision of the intradural extramedullary tumor, and internal fixation with pedicle screws. A histopathological examination confirmed that the tumor was a PIEES/PNET via an immunohistochemical study of the surgically resected tissues. Postoperatively, the patient received chemotherapy and radiotherapy. No recurrence, metastasis, or failure of internal fixation were noted at a 17-month post-surgery radiographic examination. PIEES/PNET of the thoracolumbar spine is extremely rare. Treatment is difficult because the current literature is sparse and cases are rare. Complete resection combined with chemotherapy and radiotherapy effectively reduces recurrence and metastasis.

Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1α (HIF-1α) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.

The epithelial-to-mesenchymal transition (EMT) is a reversible process that may interact with tumor immunity through multiple approaches. Increasing evidence has demonstrated the interconnections among EMT-related processes, tumor microenvironment, immune activity, as well as the potential influence on immunotherapy response. Long non-coding RNAs (lncRNAs) are emerging as critical modulators of gene expression. They can play fundamental roles in tumor immunity and act as promising biomarkers of immunotherapy response. However, the potential roles of lncRNA in the crosstalk of EMT and tumor immunity are still unclear in sarcoma. We obtained multi-omics profiling of 1440 pan-sarcoma patients from 19 datasets. Through an unsupervised consensus clustering approach, we categorized EMT molecular subtypes. We subsequently identified 26 EMT molecular subtype and tumor immune-related lncRNAs (EILncRNA) across pan-sarcoma types and developed an EILncRNA signature-based weighted scoring model (EILncSig). The EILncSig presented a favorable performance in predicting the prognosis of sarcoma, and the high-EILncSig was associated with exclusive TME characteristics with desert-like infiltration of immune cells. Multiple altered pathways, somatically mutated genes and recurrent CNV regions associated with EILncSig were identified. Notably, the EILncSig was associated with the efficacy of immune checkpoint inhibition (ICI) therapy. We additionally screened compounds such as Irinotecan that may have the potential to convert the EILncSig phenotype. By integrative analysis on multi-omics profiling, our findings provide a comprehensive resource for understanding the functional role of lncRNA-mediated immune regulation in sarcomas, which may advance the understanding of tumor immune response and the development of lncRNA-based immunotherapeutic strategies for sarcoma.

The epithelial-to-mesenchymal transition (EMT) is a reversible process that may interact with tumour immunity through multiple approaches. There is increasing evidence demonstrating the interconnections among EMT-related processes, the tumour microenvironment, and immune activity, as well as its potential influence on the immunotherapy response. Long non-coding RNAs (lncRNAs) are emerging as critical modulators of gene expression. They play fundamental roles in tumour immunity and act as promising biomarkers of immunotherapy response. However, the potential roles of lncRNA in the crosstalk of EMT and tumour immunity are still unclear in sarcoma. We obtained multi-omics profiling of 1440 pan-sarcoma patients from 19 datasets. Through an unsupervised consensus clustering approach, we categorised EMT molecular subtypes. We subsequently identified 26 EMT molecular subtype and tumour immune-related lncRNAs (EILncRNA) across pan-sarcoma types and developed an EILncRNA signature-based weighted scoring model (EILncSig). The EILncSig exhibited favourable performance in predicting the prognosis of sarcoma, and a high-EILncSig was associated with exclusive tumour microenvironment (TME) characteristics with desert-like infiltration of immune cells. Multiple altered pathways, somatically-mutated genes and recurrent CNV regions associated with EILncSig were identified. Notably, the EILncSig was associated with the efficacy of immune checkpoint inhibition (ICI) therapy. Using a computational drug-genomic approach, we identified compounds, such as Irinotecan that may have the potential to convert the EILncSig phenotype. By integrative analysis on multi-omics profiling, our findings provide a comprehensive resource for understanding the functional role of lncRNA-mediated immune regulation in sarcomas, which may advance the understanding of tumour immune response and the development of lncRNA-based immunotherapeutic strategies for sarcoma.

Reconstruction after resection has always been an urgent problem in the treatment of bone tumours. There are many methods that can be used to reconstruct bone defects; however, there are also many complications, and it is difficult to develop a safe and effective reconstruction plan for the treatment of bone tumours. With the rapid development of digital orthopaedics, three-dimensional printing technology can solve this problem. The three-dimensional printing of personalised prostheses has many advantages. It can be used to print complex structures that are difficult to fabricate using traditional processes and overcome the problems of stress shielding and low biological activity of conventional prostheses. In this study, 12 patients with bone tumours were selected as research subjects, and based on individualised reverse-engineering design technology, a three-dimensional model of each prosthesis was designed and installed using medical image data. Ti6Al4V was used as the raw material to prepare the prostheses, which were used to repair bone defects after surgical resection. The operation time was 266.43 ± 21.08 minutes (range 180-390 minutes), and intraoperative blood loss was 857.26 ± 84.28 mL (range 800-2500 mL). One patient had delayed wound healing after surgery, but all patients survived without local tumour recurrence, and no tumour metastasis was found. No aseptic loosening or structural fracture of the prosthesis, and no non-mechanical prosthesis failure caused by infection, tumour recurrence, or progression was observed. The Musculo-Skeletal Tumour Society (MSTS) score of limb function was 22.53 ± 2.09 (range 16-26), and ten of the 12 patients scored ≥ 20 and were able to function normally. The results showed that three-dimensional printed prostheses with an individualised design can achieve satisfactory short-term clinical efficacy in the reconstruction of large bone defects after bone tumour resection.

To evaluate the short-term clinical efficacy and complications of en bloc resection and intercalary prosthesis implantation for the treatment of humeral diaphyseal bone metastases. A total of 21 patients with humeral diaphyseal bone metastases treated with en bloc resection and intercalary prosthesis implantation from August 2014 to August 2019 were retrospectively analysed. The visual analogue scale (VAS), Musculoskeletal Tumour Society (MSTS) scale, International Society of Limb Salvage (ISOLS) scoring system, Karnofsky Performance Status (KPS) scale, and Nottingham Health Profile (NHP) scale were used to assess pain, limb function, and quality of life. Survival of the patients was analysed using the Kaplan-Meier method. The patients were followed up for 12–57 months (mean: 22 months); the operative time was 68–114 minutes (mean: 76.24 min); the osteotomy length was 6.5–10 cm (mean: 8.02 cm); and the intra-operative blood loss was 95–125 ml (mean: 104.71 ml). At three, six and 12 months after surgery, the VAS and NHP scores were lower, whereas the MSTS, ISOLS, and KPS scores were higher than those before surgery, and the differences were statistically significant (P

Osteosarcoma is a highly invasive kind of malignant bone tumor. Exosomes are a type of extracellular vesicles that play an important role in intercellular communication in the microenvironment. Tumor cell progression is promoted through the interaction between exosomes and cells in the microenvironment (including immune cells, mesenchymal cells, and endothelial cells) during tumor development. Neoplastic exosomes can carry a variety of biological information molecules, such as proteins, lipids, and nucleic acids. These molecules play an important clinical role, not only being able domesticate the recipient cells but also being recognized as tumor specific markers. At the same time, exosomes secreted by osteosarcoma can also cooperate with antigen-presenting cells to activate the body's immune response and then to exert anti-tumor effects. Studies on exosomes may be a breakthrough in the search for a new osteosarcoma treatment. In this study, we review the role of neoplastic exosomes in the osteosarcoma microenvironment, summarize their potential as tumor markers, and investigate their clinical application prospects.

The current global burden of tuberculosis (TB) is one of the greatest challenges to public health, particularly in developing countries, and thus effective diagnostic methods and treatment options for TB remain a central topic in basic and clinical research. Heparin-binding hemagglutinin (HBHA)-specific immune responses have been linked to protection against TB. The binding of HBHA-coated beads to epithelial and endothelial cell layers may trigger transcytosis of the beads, which is the basis for extrapulmonary dissemination. In addition, HBHA has been confirmed as a potential diagnostic marker for TB, and it is important in developing new TB vaccines and anti-TB drugs. Recently, basic research on HBHA has been intensified. The HBHA application in the field of prevention and treatment should be further explored. In addition, the existing research achievements have shown its broad application prospects. Currently, there are no relevant specialized products, and research should be accelerated. These products may contribute to the application of HBHA in the diagnosis, prevention and treatment of TB.

Human sulfatase‑1 (HSulf‑1) is emerging as a novel prognostic biomarker in breast cancer. Previous studies demonstrated HSulf‑1 to function as a negative regulator of cyclin D1 in breast cancer. Accumulating preclinical evidence is supporting the efficacy of cyclin‑dependent kinase (CDK) 4/6 inhibitors against the luminal androgen receptor sub‑type of triple‑negative breast cancer (TNBC). It was therefore hypothesized that HSulf‑1 may cooperate with CDK4/6 inhibitors to control cell cycle progression in breast cancer cells. HSulf‑1 expression was found to be downregulated in TNBC tissues and cell lines compared with that in healthy tissues and non‑breast cancer cell lines, respectively. High levels of HSulf‑1 expression was also found to be associated with increased progression‑free survival and overall survival in patients with TNBC. Functionally, it was demonstrated that HSulf‑1 served as tumor suppressor in TNBC by inducing cell cycle arrest and apoptosis whilst inhibiting proliferation, epithelial‑mesenchymal transition, migration and invasion. Subsequent overexpression of HSulf‑1 coupled with treatment with the CDK4/6 inhibitor palbociclib exhibited a synergistic antitumor effect on retinoblastoma (RB)‑positive TNBC. Further studies revealed the mechanism underlying this cooperative antiproliferative effect involved to be due to the prohibitive effects of HSulf‑1 on the palbociclib‑induced accumulation of cyclin D1 through AKT/STAT3 and ERK1/2/STAT3 signaling. Taken together, findings from the present study not only suggest that HSulf‑1 may be a potential therapeutic target for TNBC, but also indicate that combinatorial treatment could be an alternative therapeutic option for RB‑positive TNBC, which may open novel perspectives.

BackgroundSacroiliac joint tumor is rare, and the reconstruction after tumor resection is difficult. We aimed to analyze and compare the clinical effects of three-dimensional (3D) printed prostheses and bone cement combined with screws for bone defect reconstruction after sacroiliac joint tumor resection.MethodsTwelve patients with sacroiliac joint tumors who underwent tumor resection and received 3D-printed prostheses to reconstruct bone defects in our hospital from January 2014 to December 2020 were included in the study group Twelve matched patients who underwent sacroiliac joint tumor resection and reconstruction with bone cement and screws in the same time period were selected as the control group.ResultsIn the 3D-printing group, six cases were extensively excised, and six cases were marginally excised. All patients were followed up for 6–90 months, and the median follow-up time was 21 months. Among them, nine patients had disease-free survival, two survived with tumor recurrence, and one died due to tumor metastasis. The MSTS-93 score of the surviving patients was 24.1 ± 2.8. The operation time was 120.30 ± 14.50 min, and the intraoperative bleeding was 625.50 ± 30.00 ml. In the control group, seven cases were extensively excised, and five cases were marginally excised. All patients were followed up for 6–90 months, with a median follow-up time of 20 months. Among them, nine patients had disease-free survival, one survived with tumor recurrence, and two died due to tumor metastasis. The MSTS-93 score of the patients was 18.9 ± 2.6. The operation time was 165.25 ± 15.00 min, and the intraoperative bleeding was 635.45 ± 32.00 ml. There was no significant difference in survival status, intraoperative blood loss, or complications between the two groups (P>0.05). However, there were statistically significant differences in operative time and postoperative MSTS-93 scores between the two groups (PConclusionsAfter resection of the sacroiliac joint tumor, reconstruction using 3D printed prostheses was shorter and resulted in better movement function.

Circular RNA (circRNA) is important in the pathogenesis of many diseases. By analyzing the GSE96964 microarray, hsa_circ_0000285 (circ-0000285) was found to be highly expressed in osteosarcoma. Recent studies have shown that circ-0000285 is capable of regulating proliferative and migratory potentials. Here, we investigated the potential functions in regulating osteosarcoma cells to proliferate and migrate. First of all, qRT-PCR data revealed a higher level of circ-0000285 in osteosarcoma cell lines relative to normal osteoblasts. Through dual-luciferase reporter gene assay and RIP assay, we confirmed that both circ-0000285 and TGFB2 could directly bind to miRNA-599. Regulatory effects of circ-0000285 and miRNA-599 on proliferative and migratory potentials were evaluated by EdU assay and transwell migration assay. It is indicated that circ-0000285 overexpression enhanced the proliferative and migratory potentials of osteosarcoma, which could be reversed by miRNA-599 overexpression. This study revealed a vital role of circ-0000285/miRNA-599/TGFB2 axis in regulating the progression of osteosarcoma, providing a novel perspective for clarifying its pathogenesis.

Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 years. Exploring new effective second-line therapies for OS patients is a serious challenge for researchers. Quercetin, a multiple biologically active polyphenolic flavonoid, has been used in tumor therapy. However, the exact mechanism of quercetin is still unknown, which limits the application of quercetin. In the current study, we found that quercetin could inhibit JAK2 through the JH2 domain in a non-covalent manner, resulting in the inhibition of OS proliferation and immune escape via the JAK2-STAT3-PD-L1 signaling axis. More importantly, to overcome the shortcomings of quercetin, including low water solubility and low oral availability, we encapsulated it with folic acid-modified liposomes. The transportation of quercetin by folic acid-modified liposomes may provide a feasible strategy to cure OS.

Low back pain is a vital musculoskeletal disease that impairs life quality, leads to disability and imposes heavy economic burden on the society, while it is greatly attributed to intervertebral disc degeneration (IDD). However, the existing treatments, such as medicines, chiropractic adjustments and surgery, cannot achieve ideal disc regeneration. Therefore, advanced bioactive therapies are implemented, including stem cells delivery, bioreagents administration, and implantation of biomaterials etc. Among these researches, few reported unsatisfying regenerative outcomes. However, these advanced therapies have barely achieved successful clinical translation. The main reason for the inconsistency between satisfying preclinical results and poor clinical translation may largely rely on the animal models that cannot actually simulate the human disc degeneration. The inappropriate animal model also leads to difficulties in comparing the efficacies among biomaterials in different reaches. Therefore, animal models that better simulate the clinical charateristics of human IDD should be acknowledged. In addition, in vivo regenerative outcomes should be carefully evaluated to obtain robust results. Nevertheless, many researches neglect certain critical characteristics, such as adhesive properties for biomaterials blocking annulus fibrosus defects and hyperalgesia that is closely related to the clinical manifestations, e.g., low back pain. Herein, in this review, we summarized the animal models established for IDD, and highlighted the proper models and parameters that may result in acknowledged IDD models. Then, we discussed the existing biomaterials for disc regeneration and the characteristics that should be considered for regenerating different parts of discs. Finally, well-established assays and parameters for in vivo disc regeneration are explored.

Due to the rarity and heterogeneity, it is challenging to explore and develop new therapeutic targets for patients with sarcoma. Recently, immune cell infiltration in the tumor microenvironment (TME) was widely studied, which provided a novel potential approach for cancer treatment. The competing endogenous RNA (ceRNA) regulatory network has been reported as a critical molecular mechanism of tumor development. However, the role of the ceRNA regulatory network in the TME of sarcoma remains unclear. In this study, gene expression data and clinical information were obtained from The Cancer Genome Atlas (TCGA) sarcoma datasets, and an immune infiltration-related ceRNA network was constructed, which comprised 14 lncRNAs, 13 miRNAs, and 23 mRNAs. Afterward, we constructed an immune infiltration-related risk score model based on the expression of IRF1, MFNG, hsa-miR-940, and hsa-miR-378a-5p, presenting a promising performance in predicting the prognosis of patients with sarcoma.

Programmed necrosis of nucleus pulposus (NP) cells caused by excessive compression is a crucial factor in the etiopathogenesis of intervertebral disc degeneration (IVDD). The endoplasmic reticulum (ER) and mitochondria are crucial regulators of the cell death signaling pathway, and their involvement in IVDD has been reported. However, the specific role of ER stress (ERS) and ER-mitochondria interaction in compression-induced programmed necrosis of NP cells remains unknown. Our studies revealed that compression enhanced ERS and the association between ER and mitochondria in NP cells. Suppression of ERS via 4-phenylbutyrate (4-PBA) or ER-mitochondrial Ca2+ crosstalk by inhibiting the inositol 1,4,5-trisphosphate receptor, glucose-regulated protein 75, voltage-dependent anion-selective channel 1 complex (IP3R–GRP75–VDAC1 complex) protected NP cells against programmed necrosis related to the poly(ADP-ribose) polymerase (PARP) apoptosis-inducing factor (AIF) pathway. Moreover, excessive reactive oxygen species are critical activators of ERS, leading to mitochondrial Ca2+ accumulation and consequent programmed necrosis. These data indicate that ERS and ER-mitochondrial Ca2+ crosstalk may be potential therapeutic targets for the treatment of IVDD-associated disorders. These findings provide new insights into the molecular mechanisms underlying IVDD and may provide novel therapeutic targets.

The development of tissue engineering has led to new strategies for mitigating clinical problems; however, the design of the tissue engineering materials remains a challenge. The limited sources and inadequate function, potential risk of microbial or pathogen contamination, and high cost of cell expansion impair the efficacy and limit the application of exogenous cells in tissue engineering. However, endogenous cells in native tissues have been reported to be capable of spontaneous repair of the damaged tissue. These cells exhibit remarkable plasticity, and thus can differentiate or be reprogrammed to alter their phenotype and function after stimulation. After a comprehensive review, we found that the plasticity of these cells plays a major role in establishing the cell source in the mechanism involved in tissue regeneration. Tissue engineering materials that focus on assisting and promoting the natural self-repair function of endogenous cells may break through the limitations of exogenous seed cells and further expand the applications of tissue engineering materials in tissue repair. This review discusses the effects of endogenous cells, especially stem cells, on injured tissue repairing, and highlights the potential utilisation of endogenous repair in orthopaedic biomaterial constructions for bone, cartilage, and intervertebral disc regeneration.

Osteoarticular tuberculosis, a chronic inflammatory disease characterized by Mycobacterium tuberculosis (M.tb) infection, has become a serious problem in China. The present study was conducted to determine the mechanism of action of tumor necrosis factor (TNF)-α in the pathogenesis of osteoarticular tuberculosis. The number of osteoclasts in osteoarticular tuberculosis tissue samples was detected by tartrate-resistant acid phosphatase staining. Autophagy and apoptosis of osteoclasts were detected by western blotting, reverse transcription-quantitative PCR, transmission electron microscopy and TUNEL staining. The results showed that autophagy and the number of osteoclasts increased in the lesions of patients with osteoarticular tuberculosis compared with osteoarthritis samples. Moreover, activation of osteoclast autophagy inhibited the apoptosis of osteoclasts infected with M.tb, and increased the expression level of TNF-α. The results showed that TNF-α enhanced the autophagic activity of M.tb-infected osteoclasts and inhibited cell apoptosis. These findings indicated that M.tb infection induced osteoclast production and inhibited osteoclast apoptosis by regulating TNF-α-mediated osteoclast autophagy, revealing a new mechanism for TNF-α in the pathogenesis of osteoarticular tuberculosis.

Small nucleolar RNA host gene 6 (SNHG6) is a newly discovered long non-coding RNA (lncRNA), while the regulatory mechanism of SNHG6 in chondrosarcoma is largely unknown. Here we found that SNHG6 expression was upregulated and showed positive correlation with the progression of chondrosarcoma. Functional assays demonstrated that SNHG6 was required for the proliferation, migration, and invasion of chondrosarcoma cells. Mechanistic study revealed that SNHG6 could recruit EZH2 and maintain high level of H3K27me3 to repress the transcription of tumor-suppressor genes, including KLF6. KLF6 was found to bind to the promoter region of SP1 and restrained its transcription, while SP1 could be recruited to the promoter region of SNHG6 and promoted its transcription to form a positive loop. In summary, this study reveals that SP1-induced SNHG6 forms a positive loop to facilitate the carcinogenesis of chondrosarcoma through the suppression of KLF6 by recruiting EZH2, which manifests the oncogenic function of SNHG6 in chondrosarcoma.

Objective: The meta-analysis was used to evaluate the skeletal-related events (SREs) and efficacy of denosumab versus zoledronic acid (ZA) in patients with bone metastases. Methods: The data of this meta-analysis study were searched from PUBMED, EMBASE, Cochrane Library, Web of Science with Conference Proceedings, Elsevier and China National Knowledge Infrastructure (CNKI) databases till August 2017. Two independent reviewers reviewed the reference lists of relevant articles. The fixed-effects model and random-effects model were used to summarize relative estimates and 95% confidence intervals (CIs) according to the heterogeneity of the included studies. Results: Three randomized controlled trials (RCTs) including 4050 patients were identified in this meta-analysis study. The pooled analysis showed that denosumab could significantly reduce SREs, series SREs [Odds Ratio (OR) = 0.84; 95% CI, 0.74â0.95, I2 = 0%, P = 0.008] in patients with bone metastases as compared with ZA. Similar results of spinal cord compression SRE and surgery to bone SRE were obtained with (OR = 0.84; 95% CI, 0.70â1.01, I2 = 0%, P = 0.07) and (OR = 0.92; 95% CI, 0.78â1.08, I2 = 0%, P = 0.28) separately, radiation to bone SRE (OR = 0.72; 95% CI, 0.46â1.10, I2 = 11%, P = 0.13) and pathological fracture SRE (OR = 0.78; 95% CI, 0.35â1.73, I2 = 25%, P = 0.54) showed similar results, there were no significant difference between denosumab and ZA in patients with bone metastases. Conclusion: Denosumab was more effective than ZA in reducing the incidence of SRE in patients with bone metastases. Keywords: Skeletal-related event, Denosumab, Zoledronic acid, Bone metastases, Meta- analysis

Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells.Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca2+]i) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot.Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca2+]i. In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells.These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD.

// Jian-Xiang Liu 1 , Zhi-Cai Zhang 1 , Zeng-Wu Shao 1 , Fei-Fei Pu 1 , Bai-Chuan Wang 1 , Yu-Kun Zhang 1 , Xian-Lin Zeng 1 , Xiao-Dong Guo 1 , Shu-Hua Yang 1 and Tong-Chuan He 2 1 Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 2 Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago 60637, IL, USA Correspondence to: Jian-Xiang Liu, email: ljx4573@yeah.net Keywords: circulating tumor cells (CTCs), giant cell tumor of bone (GCT), TRAIL-R1 Received: March 12, 2017 Accepted: March 29, 2017 Published: April 11, 2017 ABSTRACT Giant cell tumor of bone (GCT), which frequently occurs in the patients’ spine, is relatively prevalent in Chinese population. A group of GCT invades into vessels and appears to be circulating tumor cells (CTCs) responsible for the distal metastasis of the primary tumor. So far the cell surface markers of GCT have not been determined. In the current study, we aimed to identify a novel CTC marker with higher specificity in GCT. TRAIL-R1+ cells were purified from GCT cell lines. The TRAIL-R1+ cells were compared with total GCT cells for tumor sphere formation, chemo-resistance, tumor formation in nude mice, and frequency of developing distal metastases. We found that TRAIL-R1+ GCT cells appeared to be highly enriched for CTCs in GCT. Compared to total GCT cells, TRAIL-R1+ GCT cells generated significantly more tumor spheres in culture, were higher chemo-resistant, and had a higher frequency of being detected in the circulation after subcutaneous transplantation as well as development of distal metastases. Thus, we conclude that TRAIL-R1+ may be a novel CTC marker in GCT. Selective elimination of TRAIL-R1+ GCT cells may improve the current GCT therapy.

T-cell immunoglobulin and mucin domain-containing-3 (TIM-3) performs a critical function in immune tolerance by suppressing the activation and proliferation of T cells. TIM-3 serves an important role in tumor progression in a number of carcinomas, including non-small cell lung cancer, hepatitis B virus-associated hepatocellular carcinoma, Langerhans cell sarcoma, head and neck cancer and follicular B cell non-Hodgkin lymphoma. The aim of the present study was to evaluate the possible association of TIM-3 with the prognosis of osteosarcoma. TIM-3 expression was assessed by immunohistochemical analysis in osteosarcoma tissues. The association between TIM-3 expression and prognosis was examined. To assess the association between TIM-3 expression levels and clinicopathological features, a Fisher's exact test was used. TIM-3 overexpression was indicated to be associated with surgical treatment and survival. Kaplan-Meier analysis indicated that TIM-3 is an independent predictor of overall survival, and its overexpression was indicated to be associated with poor prognosis in patients with osteosarcoma. Additionally, reverse transcription-quantitative polymerase chain reaction and western blot analysis were carried out to evaluate TIM-3 expression levels in fresh tumor tissue samples, adjacent-tissue samples, osteosarcoma cell lines, and in an osteoblastic cell line. TIM-3 was indicated to be overexpressed in fresh osteosarcoma tissue samples and in osteosarcoma cell lines. In conclusion, TIM-3 overexpression is associated with poor survival among patients with osteosarcoma and may be a possible therapeutic target in these types of tumors.

Breast cancer is a highly heterogeneous disease consisting of five disease subtypes with distinct histological characteristics, clinical behaviors and prognostic features. Stanniocalcin-1 (STC1) is a secreted glycoprotein hormone that has been demonstrated to regulate calcium and phosphate homeostasis. Mammalian STC1 is expressed in various tissues and is implicated in multiple physiological and pathophysiological processes. In addition, growing evidence has suggested that STC1 serves an oncogenic role in a number of different types of tumor. However, the role of STC1 in breast cancer is complex, considering that some studies have shown that it exerts an oncogenic role, whereas other studies have demonstrated the opposite. The aim of the present review article is to evaluate the currently available data on mammalian STC1 and discuss its potential roles in each subtype of breast cancer.

Breast cancer is a highly heterogeneous disease consisting of five disease subtypes with distinct histological characteristics, clinical behaviors and prognostic features. Stanniocalcin-1 (STC1) is a secreted glycoprotein hormone that has been demonstrated to regulate calcium and phosphate homeostasis. Mammalian STC1 is expressed in various tissues and is implicated in multiple physiological and pathophysiological processes. In addition, growing evidence has suggested that STC1 serves an oncogenic role in a number of different types of tumor. However, the role of STC1 in breast cancer is complex, considering that some studies have shown that it exerts an oncogenic role, whereas other studies have demonstrated the opposite. The aim of the present review article is to evaluate the currently available data on mammalian STC1 and discuss its potential roles in each subtype of breast cancer.

MicroRNAs are a group of small non-coding RNAs that play a complex role in post-transcriptional gene expression and can be used for diagnosis, prognosis, and targeted treatment. Despite advances in diagnosis and treatment of chondrosarcoma, its underpinning molecular mechanisms still remain elusive. Given the recent increasing knowledge base of micro RNA (miRNA) roles in neoplasia, both as oncogenes and tumor suppressor genes, this review will focus on discussing the available data on expression profiles and potential roles of miRNA in chondrosarcoma. Accumulating evidence suggests that microRNAs have the potential to be used in the future for clinical management of chondrosarcoma.

Introduction: Bone metastases lead to local bone destruction and skeletal complications. Bisphosphonates, particlulaly zoledronic acid (ZA), play a central role in the treatment of bone metastases. Some studies have shown that denosumab may delay and prevent SREs in metastatic bone disease more effectively than ZA; therefore, we systematically reviewed and assessed the safety of denosumab and ZA. Methods: The PubMed, EMBASE, Cochrane Library, Web of Science with Conference Proceedings, Elsevier, and China National Knowledge Infrastructure (CNKI) databases were searched up to October 2015. 2 independent reviewers extracted data from each eligible study using a standard protocol, and both fixed-effects and random-effects models were used to analyze and evaluate the data extracted from eligible articles. Results: 6 randomized controlled trials enrolling 13,733 patients were included. Occurrences of adverse events were generally similar between the denosumab and ZA groups except anemia and anorexia in patients with bone metastases and back pain and bone pain. However, occurrences of serious adverse events such as hypocalcaemia , renal adverse events , and new primary malignancy were significantly different between the denosumab and ZA groups. Only the occurrence of osteonecrosis of the jaw showed no significant difference between the denosumab and ZA groups in patients with bone metastases. Conclusion: Denosumab was safer in delaying or preventing skeletal-related events in patients with bone metastases and prevented pain progression compared to ZA in this meta-analysis.

The aim of the present study was to investigate the feasibility of da Vinci robotic surgery in the treatment of presacral tumors, and to observe its efficacy and safety. Between March 2016 and April 2019, 12 patients with presacral nerve sheath tumors underwent da Vinci robotic surgery, and the integrity of the tumor resection, surgical duration, pre- and postoperative visual analog scale (VAS) score, intra- and postoperative blood losses, postoperative bedtime, hospital stay and complications were observed. The tumor was completely removed in all 12 patients, the surgical duration ranged between 76 and 245 min (mean, 106.08 min) and the intraoperative blood loss was 76–145 ml (mean, 101.67 ml). The average preoperative VAS score of the patients was 3.25, and the average VAS score at 1 week, 1 month and 3 months post operation were 1.08, 0.42 and 0.08, respectively. All patients were out of bed on the second day after surgery, and the postoperative drainage was 10–50 ml (mean, 33.50 ml). The patients were hospitalized for 3–5 days (mean, 3.92 days). No complications occurred peri- or postoperatively, and wound pain was the main source of postoperative discomfort. In conclusion, the da Vinci robot can be applied to presacral nerve sheath tumors with high surgical safety, low-level bleeding, a rapid recovery and a short hospital stay, making it worthy of further study.

Background and aim To explore the diagnostic value of recombinant heparin-binding hemagglutinin adhesin (HBHA) protein antigen in spinal tuberculosis. Materials and methods Forty patients with spinal tuberculosis were included in the experimental group and 40 healthy people were included in the control group. Serum IgG antibody expression level was detected with recombinant HBHA protein as the antigen, using enzyme-linked immunosorbent assay (ELISA) detection. Results Patients with spinal tuberculosis and healthy volunteers were included in this study. A total of 40 eligible patients with spinal tuberculosis were included (24 males and 16 females, aged 18-72 years, with an average age of 41.24 ± 15.74 years). Forty healthy people were included (21 males and 19 females, aged 18-70 years, with an average age of 41.33 ± 12.36 years). On comparing the groups, no significant difference was found in the general data (P >0.05). IgG antibody level in the experimental group was higher than that in the control group, and the difference was significant (P < 0.00001). Conclusions Detection of serum HBHA protein antibody is of great value in the auxiliary diagnosis of spinal tuberculosis, and high HBHA expression can be used as an indicator for diagnosis of spinal tuberculosis.

MTH1 has become a new rising star in the field of 'cancer phenotypic lethality' and can be targeted in many kinds of tumors. This study aimed to explore the anticancer effect of MTH1-targeted drug (S)-crizotinib on osteosarcoma (OS) cells. We detected MTH1 expression in OS tissues and cells using immunohistochemistry and western blot. The effects of MTH1 on OS cell viability were explored using the siRNA technique and CCK8. The anticancer effects of the MTH1-targeted drug (S)-crizotinib on OS cells were explored by in-vitro assays. The intracellular 8-oxo-dGTP level and oxygen reactive species (ROS) of OS cells were detected by Cy3-conjugated avidin staining and dichlorofluorescein diacetate staining, respectively. The expression of MTH1 was significantly higher in OS tissues and cell lines than that in the corresponding adjacent tissues and osteoblastic cell line. The proliferation of OS cells was significantly inhibited through knockdown of MTH1 by siRNA technology. (S)-Crizotinib could inhibit the proliferation of OS cells with an increase in the apoptosis levels and causing G0/G1 arrest by targeting MTH1 and activating ROS. In addition, (S)-crizotinib could inhibit the migration of OS cells. (S)-Crizotinib could suppress the proliferation and migration, cause G0/G1 arrest, and increase the apoptosis level of OS cells by targeting MTH1 and activating ROS. This study will provide a promising therapeutic target and the theoretical basis for the clinical application of (S)-crizotinib in OS.

Prosthetic reconstruction may be a promising treatment for peri-acetabular malignant bone tumour; however, it is associated with a high complication rate. Therefore, prosthetic design and approach of prosthetic reconstruction after tumour resection warrant study. We retrospectively analyzed 11 patients with peri-acetabular malignant bone tumours treated by personalized 3D-printed hemipelvic prostheses after en bloc resection between 2015 and 2016. Pre-operative and post-operative pain at rest was assessed according to a 10-cm VAS score. The results of functional improvement were evaluated using the MSTS-93 score at the final follow-up. We also analyzed tumour recurrence, metastases, and complications associated with the reconstruction procedure. All patients were observed for six to 24 months with an average follow-up of 15.5 months. One patient had occasional pain of the involved hip at the final follow-up (VAS, pre vs. post 8 months: 3 vs. 2). The mean MSTS-93 score was 19.2 (range, 13–25). Hip dislocation was detected in two patients, while delayed wound healing occurred in one patient. One patient with mesenchymal chondrosarcoma had a left iliac bone metastasis. Local tumour recurrence was not observed. Reconstruction of bony defect after tumour resection using personalized 3D-printed hemipelvic prostheses can obtain acceptable functional results without severe complications. Based on previous reports and our results, we believe that reconstruction arthroplasty using 3D-printed hemipelvic prostheses will provide a promising alternative for those patients with peri-acetabular malignant bone tumours. Level of Evidence: Level IV, therapeutic study.

Objective To investigate the regulatory effect of post-translation modification of ribosomal protein S6 kinase 1 (S6K1) on the polyploidization of megakaryocytes. Methods SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, and H-89, a cAMP-dependent protein kinase (PKA) inhibitor, were used to treat CMK cells separately or in combination. With propidium iodide (PI) to dye DNA in the treated cells, the relative DNA content was detected by flow cytometry, and then the DNA polyploidy was analyzed. The change of expression and phosphorylation of ribosomal protein S6 kinase 1 (S6K1), an important mammalian target of rapamycin (mTOR) downstream target molecule, was analyzed by Western blotting. Molecular docking study and kinase activity assay were performed to analyze the combination of H-89 with S6K1 and the effect of H-89 on the activity of S6K1 kinase. Results SP600125 induced CMK cell polyploidization in a time-dependent and dose-dependent manner. At the same time, it increased the phosphorylation of S6K1 at Thr421/Ser424 and decreased the phosphorylation of S6K1 at Thr389. H-89 not only blocked polyploidization, but also decreased the phosphorylation of S6K1 at Thr421/Ser424 and increased the phosphorylation of S6K1 at Thr389. Molecular docking and kinase activity assay showed that H-89 occupied the ATP binding sites of S6K1 and inhibited its activity. Noticeably, both H-89 and SP600125 inhibited the activity of PKA. Moreover, the two drugs further inhibited the activity of PKA when used together. Therefore, these data indicated that H-89 blocked the SP600125-induced polyploidization of CMK cells mainly by changing S6K1 phosphorylation state, rather than its inhibitory effect on PKA. Conclusion H-89 can block the polyploidization of SP600125-induced CMK cells by regulating S6K1 phosphorylation state.

Case report. We present a rare case of a giant chordoma in the thoracolumbar spine and review the current literature. We describe its complicated clinical progression, hoping to shed light on the clinical management of this complex tumor. We present a previously healthy 41-year-old man who experienced progressive low back pain at T10-L2 for the past 2 years. A giant tumor was detected on magnetic resonance imaging, and aspiration biopsy was used to obtain a definite pathological diagnosis. The postoperative pathology confirmed that it was a chordoma. He underwent complete resection of the tumor and internal fixation of the vertebral bodies, which is a good way to control recurrence and preserve stability. Histopathology confirmed the tumor was a chordoma via immunohistochemical study of both the biopsy sample and the surgically resected tissues. There has been no recurrence or metastasis at the 30-month postsurgery radiographic examination. The internal fixation has remained stable. Primary chordoma in the thoracolumbar spine is extremely rare. The treatment is difficult because the current literature is sparse and patients are rare. Complete resection and internal fixation are effective for reducing recurrences and metastasis.

Tuberculosis is a major infectious disease that requires prolonged chemotherapy with a combination of four drugs. Here we present data suggesting that treatment of Mycobacterium tuberculosis , the causative agent of tuberculosis, and Mycobacterium smegmatis , a model organism widely used for the screening of antituberculosis agents, with first-line drugs resulted in the generation of substantial populations that could be recovered only by the addition of a culture supernatant from growing mycobacteria. These bacilli failed to grow in standard media, resulting in significant underestimation of the numbers of viable mycobacteria in treated samples. We generated M. smegmatis strains overexpressing M. tuberculosis resuscitation-promoting factors (Rpfs) and demonstrated their application for the detection of Rpf-dependent mycobacteria generated after drug exposure. Our data offer novel opportunities for validation of the sterilizing activity of antituberculosis agents.