2-Hydroxy-3-methylanthraquinone inhibits homologous recombination repair in osteosarcoma through the MYC-CHK1-RAD51 axis.

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.

Pan-sarcoma characterization of lncRNAs in the crosstalk of EMT and tumour immunity identifies distinct clinical outcomes and potential implications for immunotherapy.

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.

Anterior debridement combined with autogenous iliac bone graft fusion for the treatment of lower cervical tuberculosis: a multicenter retrospective study.

BACKGROUND: This study aimed to analyze the clinical efficacy of one-stage anterior debridement of lower cervical tuberculosis using iliac crest bone graft fusion and internal fixation. MATERIALS AND METHODS: A retrospective analysis was performed on 48 patients with lower cervical tuberculosis admitted to multiple medical centers from June 2018 to June 2021. Among them, 36 patients had lesions involving two vertebrae and 12 patients had lesions involving more than three vertebrae. All patients were treated with quadruple antituberculosis drugs for more than 2 weeks before the operation, and then treated with one-stage anterior debridement and autogenous iliac bone graft fusion combined with titanium plate internal fixation. After the operation, antituberculosis drugs were continued for 12-18 months. The patients were followed-up to observe the improvement in clinical symptoms, bone graft fusion, Cobb angle, visual analog score (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), wound healing, and neurological function. RESULTS: The patients were followed-up for 13-43 months, with an average of 21.46 ± 1.52 months. The clinical symptoms significantly improved after the operation. The bone graft was completely fused in all patients, and the bone fusion time was 3-6 months, with an average of 4.16 ± 0.47 months. At the last follow-up, the Cobb angle, VAS, ESR, and CRP level were significantly lower than those before surgery (P < 0.05). None of the patients had loosening, detachment, or rupture of the internal fixation, and no recurrence occurred. All surgical incisions healed in one stage without infection or sinus formation. The preoperative Frankel neurological function classification was grade B in 7 cases, grade C in 13, grade D in 18, and grade E in 10. At the last follow-up, 8 cases recovered to grade D and 40 recovered to grade E. CONCLUSIONS: For patients with lower cervical tuberculosis, based on oral treatment with quadruple antituberculosis drugs, direct decompression through anterior debridement, followed by autologous iliac bone graft fusion combined with internal fixation can completely remove tuberculosis foci, rebuild the stability of the cervical spine, and obtain good clinical efficacy. Level of evidence Level 3.

Quercetin encapsulated in folic acid-modified liposomes is therapeutic against osteosarcoma by non-covalent binding to the JH2 domain of JAK2 Via the JAK2-STAT3-PDL1.

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.

En bloc resection and intercalary prosthesis implantation for the treatment of humeral diaphyseal bone metastases.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.05). The survival time was four to 24 months (mean: 19.46 months). Thesix month and one year survival rates were 80.95% and 52.38%, respectively. During the follow-up period, no complications occurred except for aseptic prosthesis loosening in one patient. CONCLUSIONS: En bloc resection and intercalary prosthesis implantation can reduce pain, improve limb function, prolong survival time, and improve quality of life in patients with humeral diaphyseal bone metastases.

Total sacrectomy with a combined antero-posterior surgical approach for malignant sacral tumours.

PURPOSE: To investigate the indications, approaches, resection methods, and complications of total sacrectomy with a combined antero-posterior approach for malignant sacral tumours. METHODS: Fourteen cases of primary malignant sacral tumours treated with total sacrectomy between January 2012 and 2018 were retrospectively analysed. All patients presented with pre-operative lumbosacral pain or constipation. A combined antero-posterior approach was used for tumour resection, and the spinal pedicle screw rod system was used to achieve ilio-lumbar stability. The visual analogue scale (VAS) and Musculoskeletal Tumor Society (MSTS) scores were used to assess pain and lower limb function, respectively. The mean operative time and intra-operative blood loss were 6.54 hours and 2935 mL, respectively. The mean follow-up period was 62 months. RESULTS: None of the patients died peri-operatively. At the last follow-up, ten patients were continuously disease-free, three were alive with disease, and one died of disease from lung metastasis. Tumour recurrence occurred in three patients. The MSTS scores ranged from 6 to 28 (20.00-93.33%, 6/30-28/30) with an average of 20 (66.67%, 20/30). Seven patients could walk independently in public, five could only walk at home using a walking aid, and two could only lie down and stand for a short time. Thirteen patients developed post-operative complications such as skin necrosis, screw loosening, connecting rod fracture, neuropathic pain, sciatic nerve injury, dysuria, and urinary incontinence. CONCLUSION: Total sacrectomy can effectively treat malignant sacral tumours with good resection boundaries and prognosis. However, the high incidence of post-operative complications may impact post-operative neurological function.

Hsa_circ_0000285 functions as a competitive endogenous RNA to promote osteosarcoma progression by sponging hsa-miRNA-599.

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.

Anticancer effect of (S)-crizotinib on osteosarcoma cells by targeting MTH1 and activating reactive oxygen species.

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.

Computer-aided designed, three dimensional-printed hemipelvic prosthesis for peri-acetabular malignant bone tumour.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Giant chordoma in the thoracolumbar spine: a case report and literature review.

STUDY DESIGN: Case report. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Development of an In Vitro Assay for Detection of Drug-Induced Resuscitation-Promoting-Factor-Dependent Mycobacteria.

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.

MicroRNAs as biomarkers in the diagnosis and treatment of chondrosarcoma.

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.

Metabolite profiling of ginsenoside Rg1 after oral administration in rat.

The goal of this study is to investigate the biotransformation of ginsenoside Rg1 in vivo. A highly sensitive and specific LC-MS/MS method was developed and used for metabolite identification in rat feces and urine after oral administration of ginsenoside Rg1 . Four metabolites of Rg1 were detected in rat feces and three metabolites of Rg1 were detected in rat urine. Deglycosylation and oxygenation were found to be the major metabolic pathways of ginsenoside Rg1 after oral administration in rat. Except for the reported metabolites Rh1 and protopanaxatriol, mono-oxygenated Rg1 and mono-oxygenated protopanaxatriol were detected for the first time after oral administration of Rg1. The in vivo metabolite profiling of ginsenoside Rg1 in rat was proposed. Viewed collectively, Rg1 was metabolized to mono-oxygenated Rg1, Rh1, protopanaxatriol and the secondary metabolite mono-oxygenated protopanaxatriol in rat.

Effect of microRNA-101 on proliferation and apoptosis of human osteosarcoma cells by targeting mTOR.

Studies have proved that microRNA-101 (miR-101) functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in osteosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptosis have not been fully elucidated. In this study, we found that the expression of miR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthesized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR-101. Overexpression of miR-101 significantly decreased the expression of mTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting cells apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells. mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy by down-regulating mTOR expression.

Signalling interaction between ß-catenin and other signalling molecules during osteoarthritis development.

Osteoarthritis (OA) is the most prevalent disorder of synovial joint affecting multiple joints. In the past decade, we have witnessed conceptual switch of OA pathogenesis from a 'wear and tear' disease to a disease affecting entire joint. Extensive studies have been conducted to understand the underlying mechanisms of OA using genetic mouse models and ex vivo joint tissues derived from individuals with OA. These studies revealed that multiple signalling pathways are involved in OA development, including the canonical Wnt/ß-catenin signalling and its interaction with other signalling pathways, such as transforming growth factor ß (TGF-ß), bone morphogenic protein (BMP), Indian Hedgehog (Ihh), nuclear factor κB (NF-κB), fibroblast growth factor (FGF), and Notch. The identification of signalling interaction and underlying mechanisms are currently underway and the specific molecule(s) and key signalling pathway(s) playing a decisive role in OA development need to be evaluated. This review will focus on recent progresses in understanding of the critical role of Wnt/ß-catenin signalling in OA pathogenesis and interaction of ß-catenin with other pathways, such as TGF-ß, BMP, Notch, Ihh, NF-κB, and FGF. Understanding of these novel insights into the interaction of ß-catenin with other pathways and its integration into a complex gene regulatory network during OA development will help us identify the key signalling pathway of OA pathogenesis leading to the discovery of novel therapeutic strategies for OA intervention.

Updated roles of cGAS-STING signaling in autoimmune diseases.

Natural immunity, the first line for the body to defense against the invasion of pathogen, serves as the body's perception of the presence of pathogens depends on nucleic acid recognition mechanisms. The cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) signaling pathway is considered an essential pattern recognition and effector pathway in the natural immune system and is mainly responsible for recognizing DNA molecules present in the cytoplasm and activating downstream signaling pathways to generate type I interferons and some other inflammatory factors. STING, a crucial junction protein in the innate immune system, exerts an essential role in host resistance to external pathogen invasion. Also, STING, with the same character of inflammatory molecules, is inseparable from the body's inflammatory response. In particular, when the expression of STING is upregulated or its related signaling pathways are overactivated, the body may develop serious infectious disorders due to the generation of excessive inflammatory responses, non-infectious diseases, and autoimmune diseases. In recent years, accumulating studies indicated that the abnormal activation of the natural immune cGAS-STING signaling pathway modulated by the nucleic acid receptor cGAS closely associated with the development and occurrence of autoimmune diseases (AID). Thereof, to explore an in-depth role of STING and its related signaling pathways in the diseases associated with inflammation may be helpful to provide new avenues for the treatment of these diseases in the clinic. This article reviews the activation process of the cGAS-STING signaling pathways and its related important roles, and therapeutic drugs in AID, aiming to improve our understanding of AID and achieve better diagnosis and treatment of AID.

LncRNA MEG3 promotes chemosensitivity of osteosarcoma by regulating antitumor immunity via miR-21-5p/p53 pathway and autophagy.

This study aimed to investigate the role of long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) in chemosensitivity of osteosarcoma (OS), and to reveal the possible underlying mechanisms. In this study, we found that the expression of lncRNA MEG3 was significantly lower in OS tissues and cell lines. Furthermore, lncRNA MEG3 overexpression enhanced chemosensitivity of OS by inhibiting cell proliferation, migration, autophagy, and promoting antitumor immunity. LncRNA MEG3 functioned as miR-21-5 sponge to regulate p53 expression in OS. Mechanically, lncRNA MEG3 promoted OS chemosensitivity by regulating antitumor immunity via miR-21-5p/p53 pathway and autophagy. Collectively, this study provided the evidence that lncRNA MEG3 might be a promising therapeutic target for OS chemoresistance.

Association between total cholesterol and total bone mineral density in US adults: National Health and Nutrition Examination Survey (NHANES), 2011-2018.

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.

Clinical effect of surgical resection on primary malignant and invasive bone tumours of the proximal fibula.

There is no unified surgical plan for fibular proximal malignant tumours; therefore, the present study retrospectively analysed the medical records of 19 patients with primary malignant and invasive tumours in the proximal fibula and discussed the postoperative oncological results, complications and postoperative functions of limb salvage surgery. According to pathological classification, there were 10 osteosarcoma cases, 3 chondrosarcoma cases, 2 invasive giant cell osteosarcoma tumour cases, 1 epithelioid sarcoma case, 1 leiomyosarcoma case, 1 fibrosarcoma case and 1 lymphoma case. According to the Enneking instalment, IB stage was found in 2 cases, IIA in 2 cases and IIB in 15 cases. A total of 3 patients underwent Malawer I resection, and 16 patients underwent Malawer II resection. The follow-up period was 11-174 months, with an average of 76.58 months. Local recurrence occurred in three patients and distant metastasis in seven patients; 4 patients succumbed and 15 survived. After biceps femoris tendon reconstruction and lateral collateral ligament insertion, 18 patients had good knee stability. The Musculoskeletal Tumour Society scale ranged between 23 and 29 points, with an average of 27.26 points; the Lysholm Knee Score was 65-84 points, with an average of 83 points. After the resection of proximal fibula primary and invasive tumours, the biceps femoris tendon and lateral collateral ligament insertion point was reconstructed. The data show that this technique can effectively reconstruct stability and restore knee function.

Clinical efficacy of customized modular prosthesis in the treatment of femoral shaft metastases.

Purpose: To examine clinical outcomes of a specialized modular prosthesis used to fill a bone deficiency following removal of femoral shaft metastases. Methods: Eighteen 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. Results: The 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 (P<0.05). The survival period was between 7 and 62 months (mean, 20.89 months), and the rates of survival at 1-year and 2-year were 72.22% and 27.78%, respectively. Except for two patients with aseptic prosthesis loosening during the follow-up period, there were no problems. Conclusion: En 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.