Natural products can modulate inflammation in intervertebral disc degeneration.

Intervertebral discs (IVDs) play a crucial role in maintaining normal vertebral anatomy as well as mobile function. Intervertebral disc degeneration (IDD) is a common clinical symptom and is an important cause of low back pain (LBP). IDD is initially considered to be associated with aging and abnormal mechanical loads. However, over recent years, researchers have discovered that IDD is caused by a variety of mechanisms, including persistent inflammation, functional cell loss, accelerated extracellular matrix decomposition, the imbalance of functional components, and genetic metabolic disorders. Of these, inflammation is thought to interact with other mechanisms and is closely associated with the production of pain. Considering the key role of inflammation in IDD, the modulation of inflammation provides us with new options for mitigating the progression of degeneration and may even cause reversal. Many natural substances possess anti-inflammatory functions. Due to the wide availability of such substances, it is important that we screen and identify natural agents that are capable of regulating IVD inflammation. In fact, many studies have demonstrated the potential clinical application of natural substances for the regulation of inflammation in IDD; some of these have been proven to have excellent biosafety. In this review, we summarize the mechanisms and interactions that are responsible for inflammation in IDD and review the application of natural products for the modulation of degenerative disc inflammation.

Osteoimmunity-regulating biomaterials promote bone regeneration.

Image, graphical abstract.

Biomaterial scaffolds regulate macrophage activity to accelerate bone regeneration.

Bones are important for maintaining motor function and providing support for internal organs. Bone diseases can impose a heavy burden on individuals and society. Although bone has a certain ability to repair itself, it is often difficult to repair itself alone when faced with critical-sized defects, such as severe trauma, surgery, or tumors. There is still a heavy reliance on metal implants and autologous or allogeneic bone grafts for bone defects that are difficult to self-heal. However, these grafts still have problems that are difficult to circumvent, such as metal implants that may require secondary surgical removal, lack of bone graft donors, and immune rejection. The rapid advance in tissue engineering and a better comprehension of the physiological mechanisms of bone regeneration have led to a new focus on promoting endogenous bone self-regeneration through the use of biomaterials as the medium. Although bone regeneration involves a variety of cells and signaling factors, and these complex signaling pathways and mechanisms of interaction have not been fully understood, macrophages undoubtedly play an essential role in bone regeneration. This review summarizes the design strategies that need to be considered for biomaterials to regulate macrophage function in bone regeneration. Subsequently, this review provides an overview of therapeutic strategies for biomaterials to intervene in all stages of bone regeneration by regulating macrophages.

Risk, Prognostic Factors and Nomograms for Bone Metastasis in Young Females with Breast Cancer: A Large Cohort Retrospective Study.

Purpose: To determine the incidence of bone metastasis (BM) in young female patients with breast cancer (BC) and develop 2 robust nomograms for BM in young female patients with BC. Methods: We searched and downloaded the data from young (age ≤40 years) female patients with bone cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Univariate and multivariate analyses were performed to screen the potential diagnostic variables and prognostic factors for BM. The diagnostic and prognostic nomograms were generated and evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA). Results: A total of 13 347 young female patients with BC were identified; of these, 462 were initially diagnosed as having BM. The independent risk factors for BM in young female patients with BC were tumor size, BC subtype, American Joint Committee on Cancer (AJCC) T stage, AJCC N stage, age and marital status. The independent prognostic factors in these patients were tumor size, subtype, surgery performed, lung metastasis, liver metastasis and brain metastasis. The AUC values of the diagnostic nomogram were 0.803 (95% CI; 0.795-0.811) and 0.813 (95% CI; 0.800-0.825) in the training and validation cohorts, respectively. The time-dependent AUC values of prognostic nomogram were 0.850, 0.853, and 0.824 at 2, 3 and 4 years in the training cohort, and also >0.700 in the validation cohort. For both nomograms, the discrimination was higher than all independent variables. Calibration curve and decision curve analysis (DCA) indicated that both nomograms had favorable calibration and clinical utilization. Finally, a risk stratification system was generated and the 3 risk subgroups showed significantly distinct prognoses. Conclusions: A total of 2 nomograms were developed to assess the risk for and in prognosis of young female patients with BC with BM (BCBM).

Application of single and cooperative different delivery systems for the treatment of intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration (IDD) is the most universal pathogenesis of low back pain (LBP), a prevalent and costly medical problem across the world. Persistent low back pain can seriously affect a patient's quality of life and even lead to disability. Furthermore, the corresponding medical expenses create a serious economic burden to both individuals and society. Intervertebral disc degeneration is commonly thought to be related to age, injury, obesity, genetic susceptibility, and other risk factors. Nonetheless, its specific pathological process has not been completely elucidated; the current mainstream view considers that this condition arises from the interaction of multiple mechanisms. With the development of medical concepts and technology, clinicians and scientists tend to intervene in the early or middle stages of intervertebral disc degeneration to avoid further aggravation. However, with the aid of modern delivery systems, it is now possible to intervene in the process of intervertebral disc at the cellular and molecular levels. This review aims to provide an overview of the main mechanisms associated with intervertebral disc degeneration and the delivery systems that can help us to improve the efficacy of intervertebral disc degeneration treatment.

Application of stem cells combined with biomaterial in the treatment of intervertebral disc degeneration.

As the world population is aging, intervertebral disc degeneration (IDD) is becoming a global health issue of increasing concern. A variety of disc degeneration diseases (DDDs) have been proven to be associated with IDD, and these illnesses have significant adverse effects on both individuals and society. The application of stem cells in regenerative medicine, such as blood and circulation, has been demonstrated by numerous studies. Similarly, stem cells have made exciting progress in the treatment of IDD. However, due to complex anatomical structures and functional requirements, traditional stem cell injection makes it difficult to meet people's expectations. With the continuous development of tissue engineering and biomaterials, stem cell combined with biomaterials has far more prospects than before. This review aims to objectively and comprehensively summarize the development of stem cells combined with contemporary biomaterials and the difficulties that need to be overcome.

Development and Validation of Nomograms to Assess Risk Factors and Overall Survival Prediction for Lung Metastasis in Young Patients with Osteosarcoma: A SEER-Based Study.

Background: To establish two nomograms to quantify the diagnostic factors of lung metastasis (LM) and their role in assessing prognosis in young patients with LM osteosarcoma. Methods: A total of 618 osteosarcoma young patients from 2010 to 2015 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Another 131 patients with osteosarcoma from local hospitals were also collected as an external validation set. Patients were randomized into training sets (n = 434) and validation sets (n = 184) with a ratio of 7:3. Univariate and multivariate logistic regression analyses were used to identify the risk factor for LM and were used to construct the nomogram. Risk variables for the overall survival rate of patients with LM were evaluated by Cox regression. Another nomogram was also constructed to predict survival rates. The results were validated using bootstrap resampling and retrospective research on 131 osteosarcoma young patients from 2010 to 2019 at three local hospitals. Results: There were 114 (18.45%) patients diagnosed as LM at initial diagnosis. The multivariate logistic regression analysis suggested that T stage, N stage, and bone metastasis were independent risk factors for LM in newly diagnosed young osteosarcoma patients (P < 0.001). The ROC analysis revealed that area under the curve (AUC) values were 0.751, 0.821, and 0.735 in the training set, internal validation set, and external validation set, respectively, indicating good predictive discrimination. The multivariate Cox proportional hazard regression analysis suggested that age, surgery, chemotherapy, primary site, and bone metastasis were prognostic factors for young osteosarcoma patients with LM. The time-dependent ROC curves showed that the AUCs for predicting 1-year, 2-year, and 3-year survival rates were 0.817, 0.792, and 0.815 in the training set and 0.772, 0.807, and 0.804 in the internal validation set, respectively. As for the external validation set, the AUCs for predicting 1-year, 2-year, and 3-year survival rates were 0.787, 0.818, and 0.717. Conclusions: The nomograms can help clinicians strengthen their personal decision-making and can improve the prognosis of osteosarcoma patients.

Establishment of the diagnostic and prognostic nomograms for pancreatic cancer with bone metastasis.

Bone metastasis (BM) is rare in patients with pancreatic cancer (PC), but often neglected at the initial diagnosis and treatment. Bone metastasis is associated with a worse prognosis. This study was aimed to perform a large data analysis to determine the predictors and prognostic factors of BM in PC patients and to develop two nomograms to quantify the risks of BM and the prognosis of PC patients with BM. In the present study, we reviewed and collected the data of patients who were diagnosed as PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses were used together to screen and validate the risk factors for BM in PC patients. The independent prognostic factors for PC patients with BM were identified by Cox regression analysis. Finally, two nomograms were established via calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). This study included 16,474 PC patients from the SEER database, and 226 of them were diagnosed with BM. The risk factors of BM for PC patients covered age, grade, T stage, N stage, tumor size, and primary site. The independent prognostic factors for PC patients with BM included age, race, grade, surgery, and lung metastasis. The AUC of the diagnostic nomogram was 0.728 in the training set and 0.690 in the testing set. In the prognostic nomogram, the AUC values of 6/12/18 month were 0.781/0.833/0.849 in the training set and 0.738/0.781/0.772 in the testing set. The calibration curve and DCA furtherly indicated the satisfactory clinical consistency of the nomograms. These nomograms could be accurate and personalized tools to predict the incidence of BM in PC patients and the prognosis of PC patients with BM. The nomograms can help clinicians make more personalized and effective treatment choices.