Revealing the impact of autophagy-related genes in rheumatoid arthritis: Insights from bioinformatics.

Background: Rheumatoid arthritis is a systemic inflammatory autoimmune disease that severely impacts physical and mental health. Autophagy is a cellular process involving the degradation of cellular components in lysosomes. However, from a bioinformatics perspective, autophagy-related genes have not been comprehensively elucidated in rheumatoid arthritis. Methods: In this study, we performed differential analysis of autophagy-related genes in rheumatoid arthritis patients using the GSE93272 dataset from the Gene Expression Omnibus database. Marker genes were screened by least absolute shrinkage and selection operator. Based on marker genes, we used unsupervised cluster analysis to elaborate different autophagy clusters, and further identified modules strongly associated with rheumatoid arthritis by weighted gene co-expression network analysis. In addition, we constructed four machine learning models, random forest model, support vector machine model, generalized linear model and extreme gradient boosting based on marker genes, and based on the optimal machine learning model, a nomogram model was constructed for distinguishing between normal individuals and rheumatoid arthritis patients. Finally, five external independent rheumatoid arthritis datasets were used for the validation of our results. Results: The results showed that autophagy-related genes had significant expression differences between normal individuals and osteoarthritis patients. Through least absolute shrinkage and selection operator screening, we identified 31 marker genes and found that they exhibited significant synergistic or antagonistic effects in rheumatoid arthritis, and immune cell infiltration analysis revealed significant changes in immune cell abundance. Subsequently, we elaborated different autophagy clusters (cluster 1 and cluster 2) using unsupervised cluster analysis. Next, further by weighted gene co-expression network analysis, we identified a brown module strongly associated with rheumatoid arthritis. In addition, we constructed a nomogram model for five marker genes (CDKN2A, TP53, ATG16L2, FKBP1A, and GABARAPL1) based on a generalized linear model (area under the curve = 1.000), and the predictive efficiency and accuracy of this nomogram model were demonstrated in the calibration curves, the decision curves and the five external independent datasets were validated. Conclusion: This study identified marker autophagy-related genes in rheumatoid arthritis and analyzed their impact on the disease, providing new perspectives for understanding the role of autophagy-related genes in rheumatoid arthritis and providing new directions for its individualized treatment.

Lycium barbarum polysaccharides attenuate nonylphenol and octylphenol-induced oxidative stress and neurotransmitter disorders in PC-12 cells.

Nonylphenol (NP) and octylphenol (OP) are environmental contaminants with potential endocrine disrupting effects. However, there is limited research on the mechanisms and intervention of combined NP and OP exposure-induced neurotoxicity. This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250 µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8 µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information regulation type 1 (SIRT1), monoamine oxidase A (MAOA), phosphorylated cyclic-AMP response binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase receptor type B (p-TrkB). However, N-acetyl-L-cysteine (NAC) treatment counteracted the changes of signalling molecule p38, SIRT1/MAOA and CREB/BDNF/TrkB pathways-related proteins induced by NP and OP. LBP pretreatment ameliorated combined NP and OP exposure-induced oxidative stress and neurotransmitter imbalances. Furthermore, the application of LBP and administration of a p38 inhibitor both reversed the alterations in the signaling molecule p38, as well as the proteins associated to the SIRT1/MAOA and CREB/BDNF/TrkB pathways. These results implied that LBP may have neuroprotective effects via p38-mediated SIRT1/MAOA and CREB/BDNF/TrkB pathways.

Lycium barbarum polysaccharides attenuate oxidative stress and mitochondrial toxicity induced by mixed plasticizers in HepG2 cells through activation of Nrf2.

AIMS: In daily life, it is common for humans to be exposed to multiple phthalate esters (PAEs). However, there is limited research on the mechanisms and intervention of combined PAEs toxicity. This study aims to explore the cytotoxicity of combined PAEs and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. MAIN METHODS: LBP (62.5, 125 and 250 µg/mL) were applied to intervene HepG2 cells treated with DEHP and DBP mixtures (50, 100, 200, 400 and 800 µg/mL). Western Blot and different kits were mainly performed in our study. KEY FINDINGS: DEHP and DBP mixtures suppressed the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and activated MAPK pathway by increasing ROS. Combined DEHP and DBP exposure reduced ATP content and inhibited the mitochondrial biogenesis pathway in HepG2 cells through oxidative stress, which in turn caused cytotoxicity. LBP reduced oxidative stress and cell death induced by mixed plasticizers, upregulated Nrf2 levels and mitochondrial biogenesis pathway levels and inhibited MAPK pathway activation. Notably, after treating HepG2 cells with Nrf2-specific inhibitor (ML385, 0.5 µM), we found that the activation of Nrf2 played a crucial role on LBP intervention of DEHP and DBP induced HepG2 cytotoxicity. SIGNIFICANCE: This study not only enhances our understanding of the toxicological effects caused by combined PAEs exposure, but also has significant implications in devising strategies to mitigate the toxicological consequences of combined exposure to exogenous chemicals through the investigation of the role of LBP.

Revealing the impact of TOX3 on osteoarthritis: insights from bioinformatics.

Osteoarthritis, a prevalent long-term condition of the joints, primarily impacts older individuals, resulting in discomfort, restrictions in mobility, and a decrease in overall well-being. Although Osteoarthritis is widely spread, there is a lack of successful interventions to stop the advancement of the condition. Numerous signaling pathways have been emphasized in recent research on Osteoarthritis, yet the diagnostic significance of numerous genes has not been investigated. To identify genes that were expressed differently in osteoarthritis, we utilized the Gene Expression Omnibus database. To identify marker genes, we built machine learning models including Least Absolute Shrinkage and Selection Operator and Random Forest. We categorized Osteoarthritis samples and performed immune cell infiltration analysis based on the expression patterns of these characteristic genes. Both the Least Absolute Shrinkage and Selection Operator and Random Forest models selected six marker genes (TOX3, ARG1, CST7, RERGL, COL11A1, NCRNA00185) out of a total of 17 differentially expressed genes. The osteoarthritis samples were categorized into two groups, namely a high expression group and a low expression group, based on the median levels of TOX3 expression. Comparative analysis of these groups identified 85 differentially expressed genes, showing notable enrichment in pathways related to lipid metabolism in the group with high expression. Analysis of immune cell infiltration revealed noticeable differences in immune profiles among the two groups. The group with high expression of TOX3 showed a notable increase in Mast cells and Type II IFN Response, whereas B cells, Cytolytic activity, Inflammation-promoting cells, NK cells, pDCs, T cell co-inhibition, Th1 cells, and Th2 cells were significantly decreased. We constructed a ceRNA network for TOX3, revealing 57 lncRNAs and 18 miRNAs involved in 57 lncRNA-miRNA interactions, and 18 miRNA-mRNA interactions with TOX3. Validation of TOX3 expression was confirmed using an external dataset (GSE29746), revealing a notable increase in Osteoarthritis samples. In conclusion, our study presents a comprehensive analysis identifying TOX3 as a potential feature gene in Osteoarthritis. The distinct immune profiles and involvement in fat metabolism pathways associated with TOX3 expression suggest its significance in Osteoarthritis pathogenesis. The study establishes a basis for comprehending the intricate correlation between characteristic genes and Osteoarthritis, as well as for the formulation of individualized therapeutic approaches.

Anoikis-related genes signature development for clear cell renal cell carcinoma prognosis and tumor microenvironment.

Clear cell renal cell carcinoma (ccRCC) is one of the most common primary malignancies of the urinary tract, highly heterogeneous, and increasing in incidence worldwide. Anoikis is a specific type of programmed cell death in which solid tumor cells or normal epithelial cells that do not have metastatic properties lose adhesion to the extracellular matrix or undergo inappropriate cell adhesion-induced apoptosis. Anoikis is thought to play a critical role in tumorigenesis, maintenance, and treatment, according to an increasing amount of research. However, there is still some uncertainty regarding the general impact of anoikis-related genes (ARGs) on the prognostic importance, tumor microenvironment characteristics, and treatment reaction of ccRCC patients. For this study, we used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus datasets to access the RNA sequencing results and clinical information from ccRCC patients. 29 ARGs related to survival were found using differential analysis and univariate Cox regression analysis. The samples were then divided into two clusters that had different immune traits via unsupervised cluster analysis using 29 prognosis-associated differently expressed ARGs. Then, to build an ARGs signature, 7 genes (PLAU, EDA2R, AFP, PLG, TUBB3, APOBEC3G, and MALAT1) were found using Least Absolute Shrinkage and Selection Operator regression analysis. The new ARGs signature demonstrated outstanding prognostic capability for ccRCC patients' overall survival. In conclusion, for ccRCC patients, we created an ARGs signature that strongly connects to immunological traits and therapy response. Clinicians may find this ARGs signature helpful in developing more individualized and detailed treatment strategies for ccRCC patients.

Identifying Crucial Biomarkers in Osteoporosis and Ulcerative Colitis Through Bioinformatics Analysis of Co-expressed Genes.

Osteoporosis (OP) and ulcerative colitis (UC), prevalent immune diseases, exert a substantial socioeconomic impact globally. This study identifies biomarkers for these diseases, paving the way for in-depth research. Initially, the Gene Expression Omnibus (GEO) database was employed to analyze datasets GSE35958 and GSE87466. This analysis aimed to pinpoint co-expression differential genes (DEGs) between OP and UC. Subsequently, the Metascape database facilitated the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these DEGs' co-expression. For network construction and visualization, the STRING11.5 database along with Cytoscape 3.7.2 (Cytoscape Team, USA) were utilized to create a protein-protein interaction (PPI) network. Moreover, Cytoscape's cytoHubba plugin was instrumental in identifying the central genes, known as hub genes. In the datasets GSE35958 and GSE87466, 156 co-expressed DEGs were discovered. The PPI network, constructed using STRING11.5 and Cytoscape 3.7.2, comprises 96 nodes and 222 connections. Notably, seven hub genes were identified, namely COL6A1, COL6A2, BGN, NID1, PLAU, TGFB1, and PLAUR. These DEGs were predominantly enriched in pathways such as extracellular matrix organization and collagen-containing extracellular matrix, as per GO analysis. For diagnostic model construction and hub gene validation, datasets GSE56815 and GSE107499 from the GEO database were employed. The top five hub genes were validated. In conclusion, the hub genes identified in this study played a significant role in the early diagnosis, prevention, and treatment of OP and UC. Furthermore, they provide fresh insights into the underlying mechanisms of these diseases' development and progression.

Analysis of cuproptosis-related genes in Ulcerative colitis and immunological characterization based on machine learning.

Cuproptosis is a novel form of cell death, mediated by protein lipid acylation and highly associated with mitochondrial metabolism, which is regulated in the cell. Ulcerative colitis (UC) is a chronic inflammatory bowel disease that recurs frequently, and its incidence is increasing worldwide every year. Currently, a growing number of studies have shown that cuproptosis-related genes (CRGs) play a crucial role in the development and progression of a variety of tumors. However, the regulatory role of CRGs in UC has not been fully elucidated. Firstly, we identified differentially expressed genes in UC, Likewise, CRGs expression profiles and immunological profiles were evaluated. Using 75 UC samples, we typed UC based on the expression profiles of CRGs, followed by correlative immune cell infiltration analysis. Using the weighted gene co-expression network analysis (WGCNA) methodology, the cluster's differentially expressed genes (DEGs) were produced. Then, the performances of extreme gradient boosting models (XGB), support vector machine models (SVM), random forest models (RF), and generalized linear models (GLM) were constructed and predicted. Finally, the effectiveness of the best machine learning model was evaluated using five external datasets, receiver operating characteristic curve (ROC), the area under the curve of ROC (AUC), a calibration curve, a nomogram, and a decision curve analysis (DCA). A total of 13 CRGs were identified as significantly different in UC and control samples. Two subtypes were identified in UC based on CRGs expression profiles. Immune cell infiltration analysis of subtypes showed significant differences between immune cells of different subtypes. WGCNA results showed a total of 8 modules with significant differences between subtypes, with the turquoise module being the most specific. The machine learning results showed satisfactory performance of the XGB model (AUC = 0.981). Finally, the construction of the final 5-gene-based XGB model, validated by the calibration curve, nomogram, decision curve analysis, and five external datasets (GSE11223: AUC = 0.987; GSE38713: AUC = 0.815; GSE53306: AUC = 0.946; GSE94648: AUC = 0.809; GSE87466: AUC = 0.981), also proved to predict subtypes of UC with accuracy. Our research presents a trustworthy model that can predict the likelihood of developing UC and methodically outlines the complex relationship between CRGs and UC.

Establishment of a scoring model for the differential diagnosis of white coat hypertension and sustained hypertension.

OBJECTIVES: This study aimed to establish a scoring model for the differential diagnosis of white coat hypertension (WCH) and sustained hypertension (SHT). METHODS: This study comprised 553 adults with elevated office blood pressure, normal renal function, and no antihypertensive medications. Through questionnaire investigation and biochemical detection, 17 parameters, such as gender and age, were acquired. WCH and SHT were distinguished by 24 h ambulatory blood pressure monitoring. The participants were randomly divided into a training set (445 cases) and a validation set (108 cases). The above parameters were screened using least absolute shrinkage and selection operator regression and univariate logistic regression analysis in the training set. Afterward, a scoring model was constructed through multivariate logistic regression analysis. RESULTS: Finally, six parameters were selected, including isolated systolic hypertension, office systolic blood pressure, office diastolic blood pressure, triglyceride, serum creatinine, and cardiovascular and cerebrovascular diseases. Multivariate logistic regression was used to establish a scoring model. The R2 and area under the ROC curve (AUC) of the scoring model in the training set were 0.163 and 0.705, respectively. In the validation set, the R2 of the scoring model was 0.206, and AUC was 0.718. The calibration test results revealed that the scoring model had good stability in both the training and validation sets (mean square error = 0.001, mean absolute error = 0.014; mean square error = 0.001, mean absolute error = 0.025). CONCLUSION: A stable scoring model for distinguishing WCH was established, which can assist clinicians in identifying WCH at the first diagnosis.

Comparative transcriptome analysis provides insight into the molecular targets and signaling pathways of deer TGF-1 regulating chondrocytes proliferation and differentiation.

BACKGROUND: Chondrocytes are the only cell components in the cartilage, which has the poor regeneration ability. Thus, repairing damaged cartilage remains a huge challenge. Sika deer antlers are mainly composed of cartilaginous tissues that have an astonishing capacity for repair and renewal. Our previous study has demonstrated the transforming growth factor ß (TGF-ß1) is considered to be a key molecule involved in rapid growth, with the strongest expression in the cartilage layer. However, it remains to be clarified whether deer TGF-ß1 has significantly different function from other species such as mouse, and what is the molecular mechanism of regulating cartilage growth. METHODS: Primary chondrocytes was collected from new born mouse rib cartilage. The effect of TGF-ß1 on primary chondrocytes viability was elucidated by RNA sequencing (RNA-seq) technology combined with validation methods such as quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence assay (IFA). Differential expression genes were identified using the DEGseq package. RESULTS: Our results demonstrated that the overexpression of deer TGF-ß1 possibly promoted chondrocyte proliferation and extracellular matrix (ECM) synthesis, while simultaneously suppressing chondrocyte differentiation through regulating transcription factors, growth factors, ECM related genes, proliferation and differentiation marker genes, such as Comp, Fgfr3, Atf4, Stat1 etc., and signaling pathways such as the MAPK signaling pathway, inflammatory mediator regulation of TRP channels etc. In addition, by comparing the amino acid sequence and structures between the deer TGF-ß1 and mouse TGF-ß1, we found that deer TGF-ß1 and mouse TGF-ß1 proteins are mainly structurally different in arm domains, which is the main functional domain. Phenotypic identification results showed that deer TGF-ß1 may has stronger function than mouse TGF-ß1. CONCLUSION: ​These results suggested that deer TGF-ß1 has the ability to promote chondrogenesis by regulating chondrocyte proliferation, differentiation and ECM synthesis. This study provides insights into the molecular mechanisms underlying the effects of deer TGF-ß1 on chondrocyte viability.

Flourishing Antibacterial Strategies for Osteomyelitis Therapy.

Osteomyelitis is a destructive disease of bone tissue caused by infection with pathogenic microorganisms. Because of the complex and long-term abnormal conditions, osteomyelitis is one of the refractory diseases in orthopedics. Currently, anti-infective therapy is the primary modality for osteomyelitis therapy in addition to thorough surgical debridement. However, bacterial resistance has gradually reduced the benefits of traditional antibiotics, and the development of advanced antibacterial agents has received growing attention. This review introduces the main targets of antibacterial agents for treating osteomyelitis, including bacterial cell wall, cell membrane, intracellular macromolecules, and bacterial energy metabolism, focuses on their mechanisms, and predicts prospects for clinical applications.

Application of state-target application of painful arthritis liver and kidney deficiency: A review.

In recent years, with the progress and development of the times, our eating habits and lifestyle changes have led to an increase in gouty arthritis annually, with the main use of nonsteroidal anti-inflammatory drugs and other drugs. These drugs are highly dependent, resulting in an unresponsive state, which is easy to recur. Therefore, more and more patients choose traditional Chinese medicine (TCM) to treat them. After years of continuous exploration and rich clinical experience accumulation, Academician TongXiaolin put forward the dialectical strategy of "combination of state and target" in TCM. He believed that the deficiency of liver and kidney is transformed into a state, with uric acid as the target. Through the target prescription Simiao decoction to clever heat and moisture, replenishing liver and kidney, the target medicine Bixie (Dioscorea Tokoro Makino) to rheumatism, Shujin;Tufuling (Rhizoma Smilacis Glabrae) for detoxification, dehydration gas, Weilingxian (Radix et Rhizoma Clematidis) to rheumatism, pass meridians, and the combination of the condition and target achieves a good clinical effect.

Study on the Mechanical Properties of Perforated Steel Plate Reinforced Concrete.

In this paper, the mechanical properties of perforated steel plate reinforced concrete were studied. Through the compression test of the specimen, the failure mode, the compressive ultimate bearing capacity, and the stress−strain curve of the specimen were obtained. The results show that the compressive strength of perforated steel plate reinforced concrete is twice that of the same grade of plain concrete; through the pull-out test of the specimen, the failure mode and the ultimate uplift bearing capacity were obtained. The finite element software ANSYS was used to simulate the perforated steel plate reinforced concrete specimen, and the results show that the model is reliable. Through the range analysis method, the influence degree of the three factors of the thickness of the perforated steel plate, the hole diameter, and the hole spacing on the compressive strength and the ultimate bearing capacity of the pull-out was studied, and the optimal solution was obtained. The analysis results show that the order of the three factors on the compression and pull-out tests is: the plate thickness of the perforated steel plate > the hole diameter > the hole spacing; the optimal combination of the compressive strength of the perforated steel plate reinforced concrete specimen is that the thickness of the perforated steel plate is 0.75 mm, the diameter of the perforated steel plate is 15 mm, and the spacing of the perforated steel plate is 5 mm; the optimal combination of the ultimate bearing capacity of the pull-out is that the thickness of the steel plate with holes is 1.0 mm, the diameter of the steel plate with holes is 15 mm, and the spacing of the steel plate with holes is 15 mm.

Study on Mechanical Properties of Multi-Cavity Steel-Concrete Composite Beam.

This paper proposes a new form of composite beam: a multi-cavity steel-concrete composite beam. This composite beam uses internal perforated steel plate to connect the concrete with the steel structure, and shear connectors are no longer required, which is more suitable for industrial production. The mechanical properties of a multi-cavity steel-concrete composite beam in industrial applications are studied to avoid failures. In this paper, two multi-cavity steel-concrete composite beams with a size of 2500 mm × 200 mm × 300 mm were prepared, in which the angle of internal porous steel plate was set as 60° and 75°, respectively. A full-scale static load test was conducted on the beams to research its deformation and failure modes. The finite element software ANSYS was used to perform finite element modeling of multi-cavity steel-concrete composite beams and to analyze the influence of concrete strength, steel strength, porosity, and the angle of internal porous steel plate on the mechanical properties of composite beams. The results are as follows: before the composite beam reaches its serviceability limit state, its deformation basically shows a linear change; with the increase of load, the plastic deformation is gradually obvious, which can still provide a certain bearing capacity in the failure stage; the bearing capacity of the composite beam is positively correlated with the strength of concrete and steel, while negatively correlated with the porosity and the angle of internal porous steel plate; composite beams have large bearing capacity, good ductility and integrity.

Construction and validation of steroid-induced rabbit osteonecrosis model.

Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if appropriate treatment is not given in time. The clinical usage of high-dose steroid is one of the common causes of osteonecrosis. In several studies, the intravenous injection of steroid with or without lipopolysaccharide is the most commonly used strategy to construct osteonecrosis animal model. However, the injection dose, frequency, and interval of steroid and validation of successful model construction lack generally accepted protocol, and the survival and model formation rates are unsatisfactory. We have optimized the construction protocol of osteonecrosis animal model based on the previously reported ones and established a mature animal model of osteonecrosis for future studies.•A rabbit model of osteonecrosis was constructed by multiple injections of high-dose methylprednisolone.•The multidisciplinary biomedical examinations demonstrated the successful construction of osteonecrosis model in the rabbit.

Exploring the regulatory mechanism of osteoporosis based on intestinal flora: A review.

Osteoporosis is 1 of the common diseases of bone metabolism in clinic. With the aging of the population in China, osteoporosis is becoming more and more serious, and it has become 1 of the major public health problems. However, traditional therapies, such as calcium therapy and estrogen therapy, can cause serious adverse effects and damage to the body when ingested over a long period of time. Therefore, there is an urgent need to explore alternative therapies with less side effects in clinical practice. Intestinal flora is a hot topic of research in recent years. It has been studied in inflammatory bowel disease, diabetes, depression and so on. Recently, intestinal flora has received increasing attention in the pathways regulating bone metabolism. This paper contains a review of recent studies related to osteoporosis and gut flora in terms of its metabolites, immune, endocrine, and brain-gut axis pathways. The strong association between intestinal flora and bone metabolism suggests, to some extent, that intestinal flora can be a potential target for osteoporosis prevention and treatment, providing new ideas and therapies for the prevention and treatment of osteoporosis.

Biofunctionalized composite scaffold to potentiate osteoconduction, angiogenesis, and favorable metabolic microenvironment for osteonecrosis therapy.

Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if no appropriate treatment is performed in time. Core decompression is a general treatment modality for early osteonecrosis. However, effective bone regeneration in the necrotic area is still a significant challenge. This study developed a biofunctionalized composite scaffold (PLGA/nHA30 VEGF) for osteonecrosis therapy through potentiation of osteoconduction, angiogenesis, and a favorable metabolic microenvironment. The composite scaffold had a porosity of 87.7% and compressive strength of 8.9 MPa. PLGA/nHA30 VEGF had an average pore size of 227.6 µm and a water contact angle of 56.5° with a sustained release profile of vascular endothelial growth factor (VEGF). After the implantation of PLGA/nHA30 VEGF, various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment. Additionally, the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30 VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis. The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis.

Functional Macromolecular Adhesives for Bone Fracture Healing.

Compared with traditional internal fixation devices, bone adhesives are expected to exhibit remarkable advantages, such as improved fixation of comminuted fractures and maintained spatial location of fractured scattered bone pieces in treating bone injuries. In this review, different bone adhesives are summarized from the aspects of bone tissue engineering, and the applications of bone adhesives are emphasized. The concepts of "liquid scaffold" and "liquid plate" are proposed to summarize two different research directions of bone adhesives. Furthermore, significant advances of bone adhesives in recent years in mechanical strength, osseointegration, osteoconductivity, and osteoinductivity are discussed. We conclude this topic by providing perspectives on the state-of-the-art research progress and future development trends of bone adhesives. We hope this review will provide a comprehensive summary of bone adhesives and inspire more extensive and in-depth research on this subject.

Thunder-fire moxibustion for lumbar disc herniation: A systematic review and meta-analysis.

BACKGROUND: Lumbar disc herniation (LDH) is a common degenerative disease that severely impacts the quality of life of patients. Thunder-fire moxibustion is an ancient Chinese medicine-based external therapeutic procedure that has been employed for pain relief until this day. The focus of our study was to demonstrate the effectiveness and safety of thunder-fire moxibustion in the treatment of LDH. METHODS: The literature databases searched included the Cochrane Library, Web of Science, Springer, PubMed, Wanfang digital periodicals database, China national knowledge infrastructure, VIP, and Chinese biomedical literature database, and the search period was from database creation to March 2022. These include randomized controlled trials of Thunder-Fire moxibustion alone or in combination with other therapies for LDH. Two evaluators independently extracted data. We accessed the quality of inclusive studies through a Cochrane risk of bias tool. Meta-analyses were performed using Review Manager (Version 5.5). Data was analyzed using fixed-effects or random-effects models, depending on the heterogeneity test results. RESULTS: The meta-analysis included 17 studies involving 1344 patients with LDH. The analysis results were as follows: compared with other therapies, the efficacy of thunder-fire moxibustion was statistically significant; the total effective rate (RR = 1.20; 95%CI [1.15, 1.26]; P < .00001), the Japanese orthopaedic association score (MD = 4.42; 95%CI [4.10, 4.73]; P < .00001), the pain score (SMD = -2.66; 95% CI [-3.39, -1.94]; P < .00001). Only 2 reported no adverse events in the included literature, and the remaining had no relevant records. The quality of the evidence in the 17 papers we examined was low or very low. CONCLUSION: Thunder-Fire moxibustion is effective in relieving discomfort in patients with LDH. It has significant clinical efficacy, but there is still a need for prospective, multicentre, large-sample randomized controlled trials to enhance the clinical evidence due to the quality of included studies and methodological limitations.

[Effects of oral propranolol on urine bFGF, MMP-2, MMP-9 expression in children with proliferative infantile hemangioma].

PURPOSE: To investigate the effect of propranolol on urine bFGF, MMP-2, MMP-9 expression of children with proliferative infantile hemangioma(IH), so as to clarify the mechanism of propranolol in treating IH. METHODS: From June 2018 to June 2019, thirty-four children with proliferative IH were treated with oral propranolol. In addition, twenty-one normal children (age <12 months) were chosen as the control group. 10 mL of sterile morning urine were collected before and 2 months after oral administration of propranolol in infants with IH. All blood samples were placed in ordinary disinfection test tubes, centrifuged at 1 000 r/min for 10 min, the supernatant of urine was collected and stored separately. The urine samples of normal control group were processed in the same way. The expression levels of bFGF in the urine of children with proliferative IH before and 2 months after oral administration of propranolol and in the normal control group were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of MMP-2 and MMP-9 in the urine of children with proliferative IH before and 2 months after treatment and in the control group were detected by gelatin zymography. SPSS 22.0 software package was used to analyze the data. RESULTS: Two months after oral propranolol treatment, the concentration of bFGF in urine was significantly lower than that before treatment (P<0.01), but still significantly higher than that in the control group (P<0.05). The expression levels of MMP-2 and MMP-9 were significantly lower than those before treatment(P<0.01), but still higher than those in the control group (P<0.05). CONCLUSIONS: One of the mechanisms of propranolol in the treatment of children with proliferative IH may be through inhibiting the expression levels of bFGF, MMP-2 and MMP-9, and then inhibiting the proliferation and angiogenesis of vascular endothelial cells in IH, so as to achieve the effect of treating hemangioma. The detection of the expression levels of bFGF, MMP-2 and MMP-9 in urine can be used as the index for oral propranolol treatment of children with proliferative IH.

Polymer Scaffolds-Enhanced Bone Regeneration in Osteonecrosis Therapy.

Osteonecrosis without effective early treatment eventually leads to the collapse of the articular surface and causes arthritis. For the early stages of osteonecrosis, core decompression combined with bone grafting, is a procedure worthy of attention and clinical trial. And the study of bone graft substitutes has become a hot topic in the area of osteonecrosis research. In recent years, polymers have received more attention than other materials due to their excellent performance. However, because of the harsh microenvironment in osteonecrosis, pure polymers may not meet the stringent requirements of osteonecrosis research. The combined application of polymers and various other substances makes up for the shortcomings of polymers, and to meet a broad range of requirements for application in osteonecrosis therapy. This review focuses on various applying polymers in osteonecrosis therapy, then discusses the development of biofunctionalized composite polymers based on the polymers combined with different bioactive substances. At the end, we discuss their prospects for translation to clinical practice.