Global burden and socioeconomic impact of knee osteoarthritis: a comprehensive analysis.

Objective: To report the trend changes of the prevalence, incidence, and disability-adjusted life years (DALYs) of knee osteoarthritis (KOA) according to age, sex, sociodemographic index (SDI), and income. Methods: This analysis used estimates from the broader Global Burden of Disease (GBD) study 2019, which covered 201 countries from 1990 to 2019. National prevalence, incidence, and DALYs were shown by using ggplot2 and maps packages. Five-year intervals were used for age groupings. The Commonwealth and the World Bank income classifications were used for income grouping. Results: Globally, there were ~364.58 million prevalent cases (females: 225.16 million), 29.51 million incident cases (females: 17.53 million), and 11.53 million DALYs (females: 7.09 million) due to KOA in 2019. The Western Pacific Region had a high endemicity of ~7,319.87 cases per 100,000 people (7.64%). Japan's prevalence rate (12,610.12 cases per 100,000 population) was 10 times that of Somalia (1,178.23) in 2019. In 200 countries (except the United Arab Emirates), the prevalence, incidence, and DALY rates of KOA in 2019 were higher among females than among males and increased with age up to the oldest age group. The prevalence was highest in the high-middle SDI countries, and the incidence and DALYs were highest in the middle SDI countries. Conclusion: There was a large burden of KOA worldwide, with some notable intercountry variation. Some countries had 10 times the burden of other countries. Increasing population awareness regarding the prevalence, incidence, and DALYs of KOA with a focus on the population in the Western Pacific Region is needed, particularly for older females. informs health policy development, and contributes to improving the efficiency, equity, and effectiveness of healthcare systems.

ACSL4 accelerates osteosarcoma progression via modulating TGF-ß/Smad2 signaling pathway.

Osteosarcoma (OS) is a malignant bone sarcoma arising from mesenchymal stem cells. The biological role of Acyl-CoA synthetase long-chain family member 4 (ACSL4), recently identified as an oncogene in numerous tumor types, remains largely unclear in OS. In this study, we investigated the expression of ACSL4 in OS tissues using immunohistochemistry staining (IHC) staining of a human tissue microarray and in OS cells by qPCR assay. Our findings revealed a significant up-regulation of ACSL4 in both OS tissues and cells. To further understand its biological effects, we conducted a series of loss-of-function experiments using ACSL4-depleted MNNG/HOS and U-2OS cell lines, focusing on OS cell proliferation, migration, and apoptosis in vitro. Our results demonstrated that ACSL4 knockdown remarkably suppressed OS cell proliferation, arrested cells in the G2 phase, induced cell apoptosis, and inhibited cell migration. Additionally, a subcutaneous xenograft mice model was established to validate the in vivo impact of ACSL4, revealing ACSL4 silencing impaired tumor growth in the OS xenograft mice. Additionally, we discovered that ACSL4 could regulate the phosphorylation level of Smad2 through cooperative interactions, and treatment with a TGF-ß inhibitor weakened the promoting effects of ACSL4 overexpression. In short, ACSL4 regulated OS progression by modulating TGF-ß/Smad2 signaling pathway. These findings underscore ACSL4 as a promising therapeutic target for OS patients and contribute novel insights into the pathogenesis of OS.

What factors affect the methodological and reporting quality of clinical practice guidelines for osteoporosis? Protocol for a systematic review.

BACKGROUND: Osteoporosis is a disease with a high prevalence and low treatment rate, which poses a serious threat to the lives of patients and brings a heavy economic burden. Clinical practice guidelines (CPGs) provide vital guidance for disease management. Up to now, different countries, regions, and organizations have issued a certain number of CPGs for osteoporosis, but the recommendations in different guidelines are inconsistent. This protocol plans to evaluate the quality of the CPGs for osteoporosis and then make a comparative analysis of the recommendations in the CPGs. METHODS: Several databases including PubMed, Web of Science, Embase, and Cochrane Library, as well as the official website of relevant organizations will be searched. Screen and data extraction will be performed by two reviewers independently, and the third reviewer help to resolve the divergence between them. Using the AGREE II instrument and RIGHT checklist to assess the methodological and reporting quality of the CPGs. The extracted recommendations, including but not limited to screening, diagnosis, evaluation and treatment, will be summarized and analyzed, and the results will be presented in tabular form. Bubble charts will be used to show quality differences between CPGs and to describe the correlation between methodological and reporting quality through regression analysis. Excel, EndnoteX9 and SPSS 25.0 will be used. RESULT: To evaluate the advantages and disadvantages of the existing CPGs of osteoporosis and analyze the similarities and differences between the recommendations, the results will be published in a peer-reviewed journal. CONCLUSION: This study will provide systematic evidence for existing CPGs of osteoporosis and to provide a reference for CPGs users. PROTOCOL REGISTRATION: INPLASY 202070031.

Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13Rα2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats.

BACKGROUND: Intervertebral disc degeneration is related to tissue fibrosis. ADAMTS can degrade the important components of the ECM during the process of intervertebral disc degeneration, ultimately resulting in the loss of intervertebral disc function. sIL-13Rα2-Fc can inhibit fibrosis and slow down the degeneration process, but the mechanism involved remains unclear. OBJECTIVE: To determine the mechanism by which sIL-13Rα2-Fc inhibits ECM degradation and reduces intervertebral disc tissue fibrosis using a transcriptomics analysis. METHODS: A rat model of caudal intervertebral disc degeneration was established, and Sirius red staining was used to observe the pathological changes in the caudal intervertebral disc. Transcriptome sequencing was employed to assess the gene expression profiles of the intervertebral disc tissues in the model group and the sIL-13Rα2-Fc-treated group. Differentially expressed genes were identified and analyzed using GO annotation and KEGG pathway analyses. Real-time fluorescence quantitative PCR was used to verify the expression levels of candidate genes. The levels of GAG and HA were quantitatively assessed by ELISA, and the levels of collagen I and collagen II were analyzed by western blotting. RESULTS: Sirius red staining showed that in the model group, the annulus fibrosus was disordered, the number of breaks increased, and the type I collagen protein levels increased, whereas in the sIL-13Rα2-Fc group, the annulus fibrosus was ordered, the number of breaks decreased, and the type II collagen protein levels increased. In comparison with the model group, we identified 58 differentially expressed genes in the sIL-13Rα2-Fc group, and these were involved in 35 signaling pathways. Compared with those in the model group, the mRNA expression levels of Rnux1, Sod2, and Tnfaip6 in the IL-13Rα2-Fc group were upregulated, and the mRNA expression levels of Aldh3a1, Galnt3, Fgf1, Celsr1, and Adamts8 were downregulated; these results were verified by real-time fluorescence quantitative PCR. TIMP-1 (an ADAMTS inhibitor) and TIMP-1 combined with the sIL-13Rα2-Fc intervention increased the levels of GAG and HA, inhibited the expression of type I collagen, and promoted the expression of type II collagen. CONCLUSION: Adamts8 may participate in the degradation of ECM components such as GAG and HA and lead to an imbalance in the ECM of the intervertebral disc, resulting in intervertebral disc degeneration. sIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts8, thus maintaining the dynamic equilibrium of the ECM and ultimately delaying intervertebral disc degeneration.

Effect of sIL-13Rα2-Fc on the progression of rat tail intervertebral disc degeneration.

BACKGROUND: The incidence of degenerative disc disease caused by intervertebral disc injury is increasing annually, seriously affecting the quality of life of patients and increasing the disease burden on society. The mechanisms of intervertebral disc degeneration include changes in extracellular matrix (ECM) deposition and tissue fibrosis. sIL-13Rα2-Fc potently inhibits interleukin (IL)-13, as well as blocks related cell signaling pathways and inhibits fibrosis in certain tissues. However, it is unknown whether sIL-13Rα2-Fc inhibits fibrosis in injured intervertebral discs and slows the process of degeneration. We hypothesized that sIL-13Rα2-Fc delays the progression of intervertebral disc degeneration by inhibiting intervertebral disc fibrosis and improving ECM deposition. METHODS: A rat tail intervertebral disc degeneration model was established. Pathological changes in rat intervertebral disc tissue were observed by hematoxylin and eosin staining and Masson staining. Glycosaminoglycan (GAG), chondroitin sulfate (CS), keratan sulfate (KS), and hyaluronic acid (HA) contents were quantitatively analyzed by enzyme-linked immunosorbent assay. Type I and type II collagen expression levels were analyzed by reverse transcription-PCR and western blotting. RESULTS: Hematoxylin and eosin staining and Masson staining revealed annulus fibrosus rupture, disordered arrangement, decreased nucleus pulposus tissue, and decreased collagen fiber in the rat intervertebral disc tissue. Following treatment with sIL-13Rα2-Fc, pathological changes in the rat intervertebral disc were reduced. Rat intervertebral disc tissue showed decreased GAG, CS-KS, and (HA) contents, increased type I collagen levels, and decreased type II collagen levels in degenerated intervertebral discs. sIL-13Rα2-Fc intervention increased the contents of GAG, CS, KS, and HA; inhibited the expression of type I collagen; and promoted the expression of type II collagen. CONCLUSION: These results demonstrate that intervertebral disc degeneration is associated with tissue fibrosis. sIL-13Rα2-Fc can regulate type I and type II collagen expression levels by increasing GAG, CS, KS, and HA contents, thereby slowing the progression of intervertebral disc degeneration.