IL-1ß-mediated inflammatory responses in intervertebral disc degeneration: Mechanisms, signaling pathways, and therapeutic potential.

Intervertebral disc degeneration (IDD) has been widely recognized as the primary cause of low back pain and is one of the major chronic diseases imposing a severe socioeconomic burden worldwide. IDD is a degenerative process characterized by inflammatory responses, and its underlying pathological mechanisms remain complex. Genetic, developmental, biochemical, and biomechanical factors contribute to the development of IDD. There is a pressing need for an effective non-surgical treatment, mainly due to the lack of comprehensive understanding of the specific mechanisms involved and the effective therapeutic targets for IDD. Recently, interleukin (IL)-1ß has been recognized as an essential inflammatory factor and a key mediator of the inflammatory process in IDD. Current studies have found that IL-1ß is mainly involved in IDD by affecting the metabolism of the extracellular matrix and regulating cell death (RCD), such as apoptosis, pyroptosis, and ferroptosis (a new form of RCD). Although analysis of clinical samples from different laboratories confirmed how IL-1ß is induced in IDD, its specific signal transduction pathway, and the inflammatory role mediated in IDD remains unclear. This review describes the molecules and mechanisms involved in IL-1ß-mediated inflammatory responses, and their roles in resolving the inflammatory process in IDD. Understanding the signaling pathways involved in IL-1ß may lead to a new class of targets that promote remission for IDD patients. This review aims to provide a framework for the treatment of IDD by analyzing the signaling mechanism and function related to IL-1ß, especially in terms of inflammation, matrix metabolism, and cell death regulation.

A Review of the Role of Tendon Stem Cells in Tendon-Bone Regeneration.

Tendon-bone injuries are a prevalent health concern associated with sports and other physically demanding activities. These injuries have a limited innate healing ability, often leading to the formation of scar tissue rather than the regeneration of healthy tendon tissue. This scar tissue results from excessive fibrosis during the early healing process and often leads to reduced tendon function and an increased risk of reinjury. Traditionally, surgical reconstruction has been the primary treatment for tendon-bone injuries. However, restoring the natural structure and mechanical properties of tendons after surgical reconstruction presents a considerable challenge. Recently, the potential of stem cell therapy has been explored as an alternative treatment approach. In particular, a new type of pluripotent stem cell known as tendon stem cells (TDSCs) has been identified within tendon tissue. These cells exhibit the potential for self-renewal and multidirectional differentiation, meaning they can differentiate into fibroblasts and chondrocytes. These differentiated cells can aid in the repair and regeneration of new tissues by producing collagen and other matrix molecules that provide structural support. TDSCs have become a focal point in research for treating tendon-bone injuries and related conditions. The potential use of these cells provides a basis for both basic research and clinical applications, particularly in understanding the tendon-bone healing process and identifying factors that affect the ability of TDSCs to promote this healing. This review article aims to analyze the role of TDSCs in tendon-bone healing, understanding their therapeutic potential and contributing to the development of effective treatment strategies for tendon-bone injuries.

ITGB3 promotes cisplatin resistance in osteosarcoma tumors.

OBJECTIVE: Osteosarcoma is the most malignant and common primary bone tumor with a high rate of recurrence that mainly occurs in children and young adults. Therefore, it is vital to facilitate the development of novel effective therapeutic means and improve the overall prognosis of osteosarcoma patients via a deeper understanding of the mechanisms of chemoresistance in osteosarcoma progression. METHODS: In this research, the relationship between ITGB3 and the clinical characteristics of patients was detected through analysis of publicly available clinical datasets. The expression of ITGB3 was analysis in collected human osteosarcoma tissues. In addition, the potential functions of ITGB3 in the cisplatin resistance of osteosarcoma cells were investigated in vitro and in tumor xenotransplantation. Finally, the molecular mechanism of ITGB3 in the progression and recurrence of osteosarcoma were explored via transcriptome analysis. RESULTS: ITGB3 was identified as a potential regulator of tumorigenicity and cisplatin resistance in relapsed osteosarcoma. Furthermore, the decreased osteosarcoma cell proliferation and migration ability in ITGB3 knockout osteosarcoma cells were related to increased apoptosis and slowing cell cycle progression. In addition, ITGB3 had a positive correlation with cisplatin resistance in cells and tumor xenografts in mice. Accordingly, ITGB3 performed the functions of proliferation and cisplatin resistance in osteosarcoma through the MAPK and VEGF signaling pathways. CONCLUSION: Our results will contribute to a better understanding of the function and mechanism of ITGB3 in osteosarcoma cisplatin resistance and provide a novel therapeutic target to decrease cisplatin resistance and tumor recurrence in osteosarcoma patients.

Risk factors for postoperative medical morbidity and 3-month mortality in elderly patients with hip fracture following hip arthroplasty during COVID-19 pandemic.

BACKGROUND: The purpose of the current study was to investigate the incidence of postoperative medical complications and 3-month mortality in patients ≥ 70 years old with hip fracture following hip arthroplasty (HA) and independent risk factors associated with postoperative medical complications and 3-month mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. METHODS: A multicenter retrospective study was conducted, patients ≥ 70 years old with HA for hip fracture under general anesthesia were included during COVID-19 and before COVID-19 pandemic. The outcome was defined as postoperative medical complications and 3-month mortality. The baseline characteristics and risk factors were collected, multivariable logistic regression was used to identify independent risk factors for postoperative medical complications and 3-month mortality. RESULTS: A total of 1096 patients were included during COVID-19 pandemic and 1149 were included before COVID-19 pandemic in the study. Patients ≥ 70 years with hip fracture for HA had longer fracture to operation duration (7.10 ± 3.52 vs. 5.31 ± 1.29, P < 0.001), and the incidence of postoperative medical complications (21.90% vs. 12.53%, P < 0.001) and 3-month mortality (5.20% vs. 3.22%, P = 0.025) was higher during COVID-2019 pandemic. Multivariate logistic regression analysis showed that dementia (OR 2.73; 95% CI 1.37-5.44; P = 0.004), chronic obstructive pulmonary disease (COPD) (OR 3.00; 95% CI 1.92-4.71; P < 0.001), longer fracture to operation duration (OR 1.24; 95% CI 1.19-1.30; P < 0.001) were associated with increased risk for postoperative medical complications. COPD (OR 2.10; 95% CI 1.05-4.17; P = 0.035), dementia (OR 3.00; 95% CI 1.11-7.94; P = 0.031), postoperative medical complications (OR 4.99; 95% CI 2.68-9.28; P < 0.001), longer fracture to operation duration (OR 1.11; 95% CI 1.04-1.19; P = 0.002) were associated with increased risk for 3-month mortality. CONCLUSIONS: In conclusion, we found that postoperative medical morbidity and 3-month mortality in patients with hip fracture underwent HA were 21.90% and 5.20%, respectively, during the COVID-19. COPD, dementia and longer fracture to operation duration were associated with negative outcome in patients with hip fracture underwent HA during the COVID-19.

The Long Noncoding RNA ZEB2-AS1 Contributes to Proliferation and Epithelial-to-Mesenchymal Transition of Osteosarcoma.

Background: Long non-coding RNA Zinc finger E-box binding homeobox 2 (ZEB2) antisense RNA 1 (ZEB2-AS1) has been shown to promote tumor progression. However, the clinical significance and fundamental function role of ZEB2-AS1 in osteosarcoma (OS) has been poorly understood. Methods: The expression of ZEB2-AS1 was determined in tumor tissues and matched normal tissues from 67 OS patients using quantitative reverse transcriptase PCR analysis. Clinical value of ZEB2-AS1 was evaluated by χ2 test and Kaplan-Meier method. Cell proliferation was analyzed using CCK-8 assay, colony formation. Cell apoptosis status was determined by caspase-3 activity assay. Cell migration, invasion and epithelial-mesenchymal transition (EMT) were investigated by scratch wound healing, transwell invasion assays and Western blotting. Results: Clinical association analysis revealed that high ZEB2-AS1 expression correlated with tumor size, distant metastasis and poor prognosis of OS patients. Moreover, ZEB2-AS1 expression was identified as an independent prognostic factor for OS patients. Loss-of-function assays demonstrated that ZEB2-AS1 knockdown suppressed the proliferation and induced apoptosis in OS cells. In addition, ZEB2-AS1 knockdown inhibited cell migration, invasion, EMT of OS cells in vitro. Conclusions: Taken together, our data demonstrate that ZEB2-AS1 serves a putative oncogenic role and associates with unfavorable prognosis in OS.

Exosomes: A promising therapeutic strategy for intervertebral disc degeneration.

As a common problem all over the world, low back pain (LBP) places a huge social and economic burden on people. Intervertebral disc degeneration (IDD) is often considered to be the main cause of low back pain. The current methods of treating disc degenerative diseases mainly focus on relieving symptoms, including surgery and conservative treatment, but none of them can be treated with the etiology, which means that the normal structure of the intervertebral disc cannot be fundamentally restored. With the development of tissue engineering and regenerative medicine, exosomes from different sources, especially mesenchymal stem cell-derived exosomes (MSC-exos) as active biological substances for intercellular communication have made rapid progress due to their potency in promoting tissue regeneration. The study of exosomes in the field of treatment of IDD has yielded many surprising results. This paper mainly reviews the mechanism and function of exosomes in the study of delaying or reversing IDD, as well as gives the prospects and challenges of exosomes.

Analysis of risk factors for 90-day mortality after surgery in elderly patients with intertrochanteric fractures and a history of cardiovascular disease.

BACKGROUND: This study explored the risk factors for all-cause mortality 90 days after surgery in elderly patients with intertrochanteric fractures and a history of cardiovascular disease. METHODS: We retrospectively analyzed the clinical data of 166 elderly patients with intertrochanteric fractures who were admitted to the Department of Orthopedics of Sichuan Provincial People's Hospital (Eastern Hospital) between January 1, 2010 and December 31, 2014. Kaplan-Meier survival curve analysis and the logrank test were used to compare all-cause mortality in the 90-day postoperative period for elderly patients with intertrochanteric fractures and a history of cardiovascular disease. In addition, we used the Cox proportional hazards model to explore related risk factors and their relative hazard rate (HR). RESULTS: A multivariate Cox regression model was established for elderly patients with intertrochanteric fractures and a history of cardiovascular disease and all-cause mortality within 90 days after surgery. The risk factors suggested by the model were length of hospital stay (HR =1.07, Z=4.26, P<0.001), N-terminal pro brain natriuretic peptide (NT-proBNP) (HR =1.01, Z=4.61, P<0.001), and high-density lipoprotein (HDL) (HR =0.41, Z=2.05, P=0.042). The area under the working curve (AUC) of the Cox regression model was 0.91. The Kaplan-Meier survival curves grouped by length of stay, NT-proBNP, and HDL risk factors were significantly different (P<0.05). CONCLUSIONS: As the length of hospital stay increased, abnormally elevated NT-proBNP significantly increased all-cause mortality within 90 days after surgery, while elevated HDL significantly reduced patient mortality. The results of our study suggested that the combination of these 3 indicators could be used as a sensitive predictor for prognosis in elderly patients with intertrochanteric fracture surgery and a history of cardiovascular disease.

Factors associated with 90-day acute ischemic stroke in patients ≥70 years old with total hip arthroplasty for hip fracture.

BACKGROUND: Postoperative ischemic stroke is a devastating complication following total hip arthroplasty (THA). The purpose of the current study was to investigate the incidence of postoperative acute ischemic stroke (AIS) in patients ≥70 years old with THA for hip fracture after 90 days and independent risk factors associated with 90-day AIS. METHODS: A multicenter retrospective study was conducted, patients ≥70 years old with THA for hip fracture under general anesthesia were included from February 2017 to March 2020. Patients with AIS within 90 days after THA were identified as AIS group; patients with no AIS were identified as no AIS group. The baseline characteristics and risk factors were collected, multivariable logistic regression was used to identify independent risk factors of 90-dayAIS. RESULTS: 2517 patients (mean age 76.18 ± 6.01) were eligible for inclusion in the study. 2.50% (63/2517) of patients had 90-day AIS. Compared with no AIS, older age, diabetes, hyperlipidemia, atrial fibrillation (AF) and higher D-dimer value were more likely in patients with AIS (P < 0.05), and anticoagulant use was fewer in patients with AIS. ROC curve analysis showed that the optimal cut point of D-dimer for AIS was D-dimer≥4.12 µg/ml. Multivariate logistic regression analysis showed that D-dimer≥4.12 µg/ml [adjusted odds ratio (aOR), 4.44; confidence interval (CI), 2.50-7.72; P < 0.001], older age (aOR, 1.08; 95%CI, 1.03-1.12; P < 0.001), hyperlipidemia (aOR, 2.28; 95%CI, 1.25-4.16; P = 0.007), atrial fibrillation (aOR, 5.84; 95% CI, 1.08-15.68; P = 0.001), and diabetes (aOR, 2.60; 95% CI, 1.56-4.39; P < 0.001) were associated with increased risk of 90-day AIS after THA. CONCLUSIONS: In conclusion, we found that the incidence of 90-day AIS in patients≥70 years old with THA for hip fracture was 2.5%. Older age, diabetes, hyperlipidemia, AF and higher D-dimer value were independent risk factors for 90-day AIS in patients≥70 years old with THA for hip fracture.

Up-regulation of long non-coding RNA CYTOR induced by icariin promotes the viability and inhibits the apoptosis of chondrocytes.

BACKGROUND: Icariin (ICAR) is the main effective component extracted from epimedium, and is reported to have the potential to treat osteoarthritis (OA). However, its pharmacological function on chondrocytes has not been fully clarified. METHODS: Different doses of ICAR were used to treat chondrocyte cell lines, including CHON-001 and ATDC5. Then the expressions of different lncRNAs were measured by qRT-PCR. Interleukin-1ß (IL-1ß) was used to simulate the inflammatory response environment of chondrocytes. Overexpression plasmids and short hairpin RNAs of lncRNA CYTOR were used to construct gain-of-function and loss of function models. CCK-8 was conducted to determine the cell viability. Flow cytometry was used to detect the apoptosis of chondrocytes. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the contents of inflammatory factors (IL-6, IL-8, TNF-α) in the supernatant of the chondrocytes. RESULTS: Compared with other lncRNAs, CYTOR was changed most significantly in both CHON-001 and ATDC5 cells after treatment with ICAR. ICAR promotes the viability and inhibits the apoptosis of CHON-001 and ATDC5 cells induced by IL-1ß, accompanied with reduced levels of inflammatory factors. Overexpression of CYTOR facilitated the viability of chondrocytes, while repressed their apoptosis and inflammatory response. What's more, knockdown of CYTOR reversed the protective effects of ICAR on chondrocytes. CONCLUSION: CYTOR was a pivotal lncRNA involved in the protective function of ICAR on chondrocytes.

Association between increased neutrophil-to-lymphocyte ratio and postoperative delirium in elderly patients with total hip arthroplasty for hip fracture.

BACKGROUND: Delirium is a common complication in elderly patients with total hip arthroplasty (THA) for hip fracture. The mechanism of postoperative delirium (POD) is associated with the neuroinflammatory process. The aim of this study was to the incidence and perioperative risk factors of POD and investigate whether NLR could serve as a potential marker for POD in elderly patients with THA for hip fracture. METHODS: This was a multicenter prospective study, we included elderly patients with THA for hip fracture under general anesthesia. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut point of NLR for POD. The relationship between NLR and POD was analyzed by multivariable analysis. RESULTS: Seven hundred eighty patients (mean age 73.33 ± 7.66) were eligible for inclusion in the study. 23.33% (182/780) of patients had POD. ROC curve analysis showed that the optimal cut point of NLR for POD was NLR ≥ 3.5. Compared with no POD, higher NLR, older age, diabetes, and higher neutrophil count were more likely in patients with POD(P < 0.05). Multivariate logistic regression analysis showed that NLR ≥ 3.50 [adjusted odds ratio(aOR), 3.93; confidence interval (CI), 2.47-6.25; P < 0.001)], older age (aOR, 1.04; 95%CI, 1.02-1.07; P = 0.001), diabetes (aOR, 1.58; 95% CI, 1.06-2.36; P = 0.025),higher neutrophil count (aOR, 1.25; 95%CI, 1.15-1.35; P < 0.001) were associated with increased risk of POD. CONCLUSIONS: Older age, diabetes, higher neutrophil count, and NLR ≥ 3.5 were independent risk factors for POD, and NLR can be used as a potential marker for prediction of delirium in elderly patients with THA for hip fracture.

Acupotomy for nerve entrapment syndrome: A systematic review protocol.

BACKGROUND: Acupotomy has been widely used to treat nerve entrapment syndrome. But its efficiency has not been scientifically and methodically evaluated. The aim of this study is to evaluate the efficacy and safety of the acupotomy treatment in patients with nerve entrapment syndrome. METHODS: Fifteen databases will be searched from inception to Dec 2019. We will include randomized controlled trials (RCTs) assessing acupotomy for nerve entrapment syndrome. All RCTs on acupotomy or related interventions will be included. Study inclusion, data extraction and quality assessment will be performed independently by 2 reviewers. Assessment of risk of bias and data synthesis will be performed using RevMan 5.3 software. Cochrane criteria for risk-of-bias will be used to assess the methodological quality of the trials. RESULTS: This study will provide a high-quality synthesis of pain VAS and functional disability or the quality of life, the success treatment rate, the recurrent rate and the complications rate to assess the effectiveness and safety of acupotomy for nerve entrapment syndrome patients. CONCLUSION: This systematic review will provide evidence to judge whether acupotomy is an effective intervention for patients with nerve entrapment syndrome. PROSPERO REGISTRATION NUMBER: CRD42018109086.

A comparison between acupotomy vs the local steroid injection for the management of soft tissue disorder: A systematic review protocol.

BACKGROUND: This systematic review protocol aims to provide the methods used to evaluate the effectiveness of acupotomy therapy for treating soft tissue disorder comparing to local steroid injection. METHODS: Fifteen databases will be searched from inception to Dec 2019. We will include randomized controlled trials (RCTs) assessing acupotomy for soft tissue disorder. All RCTs on acupotomy or related interventions will be included. Study inclusion, data extraction and quality assessment will be performed independently by two reviewers. Assessment of risk of bias and data synthesis will be performed using RevMan 5.3 software. Cochrane criteria for risk-of-bias will be used to assess the methodological quality of the trials. RESULTS: This study will provide a high-quality synthesis of pain visual analog scale and functional disability or the quality of life, the success treatment rate, the recurrent rate, and the complications rate to assess the effectiveness and safety of acupotomy for soft tissue disorder patients compare to local steroid injection. CONCLUSION: This systematic review will provide evidence to judge whether acupotomy is an effective intervention for patients with soft tissue disorder. PROSPERO REGISTRATION NUMBER: CRD42018109080.

[Clinical application of atlas translaminar screws fixation in treatment of atlatoaxial instability].

OBJECTIVE: To explore the effectiveness of fixation of atlas translaminar screws in the treatment of atlatoaxial instability. METHODS: A retrospective analysis was made on the clinical data of 32 patients with atlatoaxial instability treated with atlantoaxial trans-pedicle screws between March 2007 and August 2009. Of them, 7 patients underwent atlas translaminar screws combined with axis transpedicle screws fixation because of fracture types, anatomic variation, and intraoperative reason, including 5 males and 2 females with an average age of 48.2 years (range, 35-69 years). A total of 9 translaminar screws were inserted. Injury was caused by traffic accident in 4 cases, falling from height in 2 cases, and crushing in 1 case. Two cases had simple odontoid fracture (Anderson type II), and 5 cases had odontoid fracture combined with other injuries (massa lateralis atlantis fracture in 2, atlantoaxial dislocation in 1, and Hangman fracture in 2). The interval between injury and operation was 4-9 days (mean, 6 days). The preoperative Japanese Orthopaedic Association (JOA) score was 8.29 +/- 1.60. RESULTS: The X-ray films showed good position of the screws. Healing of incision by first intention was obtained, and no patient had injuries of the spinal cord injury, nerve root, and vertebral artery. Seven cases were followed up 9-26 months (mean, 14 months). Good bone fusion was observed at 8 months on average (range, 6-11 months). No loosening, displacement, and breakage of internal fixation, re-dislocation and instability of atlantoaxial joint, or penetrating of pedicle screw into the spinal canal and the spinal cord occurred. The JOA score was significantly improved to 15.29 +/- 1.38 at 6 months after operation (t = 32.078, P = 0.000). CONCLUSION: Atlas translaminar screws fixation has the advantages of firm fixation, simple operating techniques, and relative safety, so it may be a remedial measure of atlatoaxial instability.