Global trends in research of venous thromboembolism associated with lower limb joint arthroplasty: A bibliometric analysis.

This study aims to visualize publications related to venous thromboembolism (VTE) and lower limb joint arthroplasty to identify research frontiers and hotspots, providing references and guidance for further research. We retrieved original articles published from 1985 to 2022 and their recorded information from the Web of Science Core Collection. The search strategy used terms related to knee or hip arthroplasty and thromboembolic events. Microsoft Excel was used to analyze the annual publications and citations of the included literature. The rest of the data were analyzed using the VOSviewer, citespace and R and produced visualizations of these collaborative networks. We retrieved 3543 original articles and the results showed an overall upward trend in annual publications. The United States of America had the most significant number of publications (Np) and collaborative links with other countries. McMaster University had the greatest Np. Papers published by Geerts WH in 2008 had the highest total link strength. Journal of Arthroplasty published the most articles on the research of VTE associated with lower limb joint arthroplasty. The latest research trend mainly involved "general anesthesia" "revision" and "tranexamic acid." This bibliometric study revealed that the research on VTE after lower limb joint arthroplasty is developing rapidly. The United States of America leads in terms of both quantity and quality of publications, while European and Canadian institutions and authors also make significant contributions. Recent research focused on the use of tranexamic acid, anesthesia selection, and the VTE risk in revision surgeries.

Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application.

Triazole demonstrates distinctive physicochemical properties, characterized by weak basicity, various dipole moments, and significant dual hydrogen bond acceptor and donor capabilities. These features are poised to play a pivotal role in drug-target interactions. The inherent polarity of triazole contributes to its lower logP, suggesting the potential improvement in water solubility. The metabolic stability of triazole adds additional value to drug discovery. Moreover, the metal-binding capacity of the nitrogen atom lone pair electrons of triazole has broad applications in the development of metal chelators and antifungal agents. This Perspective aims to underscore the unique physicochemical attributes of triazole and its application. A comparative analysis involving triazole isomers and other heterocycles provides guiding insights for the subsequent design of triazoles, with the hope of offering valuable considerations for designing other heterocycles in medicinal chemistry.

Current therapy in amyotrophic lateral sclerosis (ALS): A review on past and future therapeutic strategies.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the first and second motoneurons (MNs), associated with muscle weakness, paralysis and finally death. The exact etiology of the disease still remains unclear. Currently, efforts to develop novel ALS treatments which target specific pathomechanisms are being studied. The mechanisms of ALS pathogenesis involve multiple factors, such as protein aggregation, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, apoptosis, inflammation etc. Unfortunately, to date, there are only two FDA-approved drugs for ALS, riluzole and edavarone, without curative treatment for ALS. Herein, we give an overview of the many pathways and review the recent discovery and preclinical characterization of neuroprotective compounds. Meanwhile, drug combination and other therapeutic approaches are also reviewed. In the last part, we analyze the reasons of clinical failure and propose perspective on the treatment of ALS in the future.

Eligibility for knee arthroplasty is associated with increased risk of acquired hallux valgus - a Mendelian randomized study.

OBJECTIVE: Clinically, it has been found that patients undergoing knee replacement have a high incidence of concomitant hallux valgus. In this study, we analyzed whether patients with osteoarthritis who underwent surgery and those patient who did not have surgery had an increased risk of hallux valgus by Mendelian randomization and performed reverse causal analysis. DESIGN: Genomewide association study (GWAS) data for osteoarthritis, categorized by knee arthritis with joint replacement, knee arthritis without joint replacement, hip arthritis with joint replacement, and hip arthritis without joint replacement.And acquired hallux valgus were downloaded for Mendelian randomized studies. MR analysis was performed using inverse variance-weighted (IVW), weighted median, and MR-Egger methods. MR-egger regression, MR pleiotropic residuals and outliers (MR-presso), and Cochran's Q statistical methods were used to evaluate heterogeneity and pleiotropy. RESULTS: The IVW results indicate that, compared to healthy individuals, patients who meet the criteria for knee osteoarthritis joint replacement surgery have a significantly higher risk of acquired hallux valgus. There were no significant causal relationships found for the remaining results. No significant heterogeneity or multiplicity was observed in all the Mr analyses. CONCLUSION: Our study supports the increased risk of acquired hallux valgus in patients eligible for knee replacement. There is necessary for clinicians to be concerned about the hallux valgus status of patients undergoing knee arthroplasty.

Early exercise intervention promotes myelin repair in the brains of ischemic rats by inhibiting the MEK/ERK pathway.

Our previous studies have shown that early exercise intervention after stroke increases neural activity and synaptic plasticity and promotes the recovery of nerve fiber bundle integrity in the brain. However, the effect of exercise on the repair of myelin in the brain and the related mechanism are still unclear. In this study, we randomly divided the rats into three groups. Before and after 28 days of intervention, body weight, nerve function, the infarct size, white matter fiber bundle integrity, and nerve myelin structure and function were observed by measuring body weight, analysis of modified neurological severity score, CatWalk gait analysis, MRI, luxol fast blue staining, immunofluorescence, and transmission electron microscopy. Changes in the expression of proteins in the MEK/ERK pathway were assessed. The results showed that early exercise intervention resulted in neurological recovery, decreased the infarct volume and increased nerve fiber integrity, the myelin coverage area, myelin basic protein (MBP) fluorescence intensity expression, and myelin thickness. Furthermore, the expression level of MBP was significantly increased after early exercise intervention, while the expression levels of p-MEK1/2 and p-ERK1/2 were significantly reduced. In the cell study, MBP expression levels were significantly higher in the oxygen and glucose deprivation and administration group.In summary, early exercise intervention after stroke can promote myelin repair by inhibiting the MEK/ERK signaling pathway.

Dexamethasone Induced Osteocyte Apoptosis in Steroid-Induced Femoral Head Osteonecrosis through ROS-Mediated Oxidative Stress.

OBJECTIVE: Glucocorticoid (GC) overuse is strongly associated with steroid-induced osteonecrosis of the femoral head (SINFH). However, the underlying mechanism of SINFH remains unclear. This study aims to investigate the effect of dexamethasone (Dex)-induced oxidative stress on osteocyte apoptosis and the underlying mechanisms. METHODS: Ten patients with SINFH and 10 patients with developmental dysplasia of the hips (DDH) were enrolled in our study. Sixty rats were randomly assigned to the Control, Dex, Dex + N-Acetyl-L-cysteine (NAC), Dex + Dibenziodolium chloride (DPI), NAC, and DPI groups. Magnetic resonance imaging (MRI) was used to examine edema in the femoral head of rats. Histopathological staining was performed to assess osteonecrosis. Immunofluorescence staining with TUNEL and 8-OHdG was conducted to evaluate osteocyte apoptosis and oxidative damage. Immunohistochemical staining was carried out to detect the expression of NOX1, NOX2, and NOX4. Viability and apoptosis of MLO-Y4 cells were measured using the CCK-8 assay and TUNEL staining. 8-OHdG staining was conducted to detect oxidative stress. 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining was performed to measure reactive oxygen species (ROS). The expression of NOX1, NOX2, and NOX4 in MLO-Y4 cells was analyzed by Western blotting. Multiple comparisons were performed using one-way analysis of variance (ANOVA). RESULTS: In patients and the rat model, hematoxylin-eosin (HE) staining revealed a significantly higher rate of empty lacunae in the SINFH group than in the DDH group. Immunofluorescence staining indicated a significant increase in TUNEL-positive cells and 8-OHdG-positive cells in the SINFH group compared to the DDH group. Immunohistochemical staining demonstrated a significant increase in the expression of NOX1, NOX2, and NOX4 proteins in SINFH patients compared to DDH patients. Moreover, immunohistochemical staining showed a significant increase in the proportion of NOX2-positive cells compared to the Control group in the femoral head of rats. In vitro, Dex significantly inhibited the viability of osteocyte cells and induced apoptosis. After Dex treatment, the intracellular ROS level increased. However, Dex treatment did not alter the expression of NOX proteins in vitro. Additionally, NAC and DPI inhibited the generation of intracellular ROS and partially alleviated osteocyte apoptosis in vivo and in vitro. CONCLUSION: This study demonstrates that GC promotes apoptosis of osteocyte cells through ROS-induced oxidative stress. Furthermore, we found that the increased expression of NOXs induced by GC serves as an important source of ROS generation.

Causal association of epigenetic aging and osteoporosis: a bidirectional Mendelian randomization study.

BACKGROUND: The relationship between aging and osteoporosis is well established. However, the relationship between the body's physiological age, i.e. epigenetic age, and osteoporosis is not known. Our goal is to analyze the bidirectional causal relationship between epigenetic clocks and osteoporosis using a bidirectional Mendelian randomization study. METHODS: We used SNPs closely associated with GrimAge, Hannum, PhenoAge, and HorvathAge in epigenetic age and SNPs closely associated with femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density as instrumental variables, respectively, using the inverse variance weighting method and several other MR methods to assess the bidirectional causal relationship between epigenetic age and osteoporosis. RESULT: There was no evidence of a clear causal relationship of epigenetic age (GrimAge, Hannum, PhenoAge, and HorvathAge) on femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density. In reverse Mendelian randomization analysis showed a significant causal effect of lumbar spine bone mineral density on GrimAge: odds ratio (OR) = 0.692, 95% confidence interval (CI) = (0.538-0.890), p = 0.004. The results suggest that a decrease in lumbar spine bone mineral density promotes an acceleration of GrimAge. CONCLUSION: There was no significant bidirectional causal relationship between epigenetic age and osteoporosis A decrease in lumbar spine bone density may lead to an acceleration of the epigenetic clock "GrimAge". Our study provides partial evidence for a bidirectional causal effect between epigenetic age and Osteoporosis.

Inhibition of Son of Sevenless Homologue 1 (SOS1): Promising therapeutic treatment for KRAS-mutant cancers.

Kristen rat sarcoma (KRAS) is one of the most common oncogenes in human cancers. As a guanine nucleotide exchange factor, Son of Sevenless Homologue 1 (SOS1) represents a potential therapeutic concept for the treatment of KRAS-mutant cancers because of its activation on KRAS and downstream signaling pathways. In this review, we provide a comprehensive overview of the structure, biological function, and regulation of SOS1. We also focus on the recent advances in SOS1 inhibitors and emphasize their binding modes, structure-activity relationships and pharmacological activities. We hope that this publication can provide a comprehensive compendium on the rational design of SOS1 inhibitors.

Apocynin exerts cytoprotective effects on dexamethasone-induced osteoblasts by inhibiting oxidative stress through the Nrf2 signalling pathway.

Steroid-induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast apoptosis and osteogenic differentiation dysfunction caused by GC-induced oxidative stress and mitochondrial impairment are strongly implicated in SIFHN. Apocynin (APO) is a kind of acetophenone extracted from an herb. In recent years, APO has received much attention for its antiapoptotic and antioxidant properties. This study aimed to investigate whether APO could protect against SIFHN and explore the mechanism. In our study, low-dose APO had no toxic effects on osteoblasts and restored dexamethasone (Dex)-treated osteoblasts by improving survival, inhibiting OS and restoring mitochondrial dysfunction. Mechanistically, APO alleviated Dex-induced osteoblast injury by activating the Nrf2 pathway, and the use of ML385 to block Nrf2 significantly eliminated the protective effect of APO. In addition, APO could reduce the formation of empty lacunae, restore bone mass and promote the expression of Nrf2 in SIFHN rats. In conclusion, APO protects osteoblasts from Dex-induced oxidative stress and mitochondrial dysfunction through activation of the Nrf2 pathway and may be a beneficial drug for the treatment of SIFHN.

Multiscale Relaxation Behavior of Amorphous Plasticized Poly(vinyl butyral).

As a key component in laminated glass, plasticized polyvinyl butyral (PVB) interlayer is a kind of impact-resistant polymer material with high toughness. Recently, by using ultrasmall angle X-ray scattering (USAXS) technique, Stretch-induced phase-separated structure on the scale of hundreds of nanometers formed in plasticized PVB for the first time is reported. In this work, the multiscale relaxation behavior of plasticized PVB is further investigated. The relaxation behavior of deformed plasticized PVB is studied from macroscopic stress, mesoscopic phase-separated structure, and microscopic chain segment by combining USAXS, and birefringence with in situ stretching device. The contributions of chain segments and hydrogen bonding clusters for the multiscale relaxation behavior are discussed.

Study on the flocculation mechanism of a bioflocculant from Acinetobacter sp. TH40 combined with graphene oxide for the removal of metal ions from water.

In order to realize the simultaneous removal of nine metal ions from water, in this study, an excellent flocculant suitable for the simultaneous removal of multiple metal ions in water was developed by using the excellent flocculation properties of graphene oxide (GO) combined with biological flocculants. First, this study investigated the concentrations and pollution levels of nine metal pollutants in surface water and groundwater of a typical city in central China. The maximum concentrations of these nine metal ions were Al 0.29, Ni 0.0325, Ba 0.948, Fe 1.12, As 0.05, Cd 0.01, Zn 1.45, Mn 1.24, and Hg 0.16 (in mg/L). Second, the three-dimensional structure diagram of GO was established. Gaussian16W software and the pm6D3 semi-empirical method were used to analysis the structure and the vibration of GO. The B3LYP function and basis set DEF2SVP was used to calculate the single point energy. Third, with varying the flocculation time, it was found that the maximum flocculation efficiency could reach more than 80.00% under the optimal conditions, that is, with a metal ion mixture of 20 mg/L. The optimal dosage of GO was 15 mg/L. The optimal time for bioflocculation efficiency was 2.5 h, and the optimal concentration of bioflocculant was 3 mg/L. The optimal flocculation efficiency was 82.01% under the optimal conditions.

Causal relationships between COVID-19 and osteoporosis: a two-sample Mendelian randomization study in European population.

Introduction: The causal relationship between Coronavirus disease 2019 (COVID-19) and osteoporosis (OP) remains uncertain. We aimed to assess the effect of COVID-19 severity (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, and severe COVID-19) on OP by a two-sample Mendelian randomization (MR) study. Methods: We conducted a two-sample MR analysis using publicly available genome-wide association study (GWAS) data. Inverse variance weighting (IVW) was used as the main analysis method. Four complementary methods were used for our MR analysis, which included the MR-Egger regression method, the weighted median method, the simple mode method, and the weighted mode method. We utilized the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) global test to identify the presence of horizontal pleiotropy. Cochran's Q statistics were employed to assess the existence of instrument heterogeneity. We conducted a sensitivity analysis using the leave-one-out method. Results: The primary results of IVW showed that COVID-19 severity was not statistically related to OP (SARS-CoV-2 infection: OR (95% CI) = 0.998 (0.995 ~ 1.001), p = 0.201403; COVID-19 hospitalization: OR (95% CI) =1.001 (0.999 ~ 1.003), p = 0.504735; severe COVID-19: OR (95% CI) = 1.000 (0.998 ~ 1.001), p = 0.965383). In addition, the MR-Egger regression, weighted median, simple mode and weighted mode methods showed consistent results. The results were robust under all sensitivity analyses. Conclusion: The results of the MR analysis provide preliminary evidence that a genetic causal link between the severity of COVID-19 and OP may be absent.

PD-1/PD-L1 Inhibitor Plus Chemotherapy Versus PD-1/PD-L1 Inhibitor in Microsatellite Instability Gastrointestinal Cancers: A Multicenter Retrospective Study.

PURPOSE: To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti-PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers. METHODS: We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti-PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti-PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti-PD-1/PD-L1 group). Propensity score-based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models. RESULTS: A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti-PD-1/PD-L1 and anti-PD-1/PD-L1, respectively. The chemo-anti-PD-1/PD-L1 group showed significant improvements versus the anti-PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti-PD-1/PD-L1 versus anti-PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis. CONCLUSION: Chemo-anti-PD-1/PD-L1 is superior to anti-PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.

MPs-ACT, an Assay to Evaluate the Procoagulant Activity of Microparticles.

The procoagulant effect of microparticles (MPs) contributes to hypercoagulability-induced thrombosis. We provide preliminary findings of the MPs-Activated Clotting Time (MPs-ACT) assay to determine the procoagulant activity of MPs. MPs-rich plasma was obtained and recalcified. Changes in plasma viscoelasticity were evaluated and the time to the peak viscoelastic changes was defined as the MPs-ACT. MPs concentration was measured by flow cytometry. Coagulation products produced during plasma clotting were identified by fibrin and fibrinopeptide A. MPs were prepared in vitro and added to standard plasma to simulate pathological samples. In addition, reproducibility and sensitivity were evaluated. We confirmed the linear relationship between MPs-ACT and MP concentrations. Dynamic changes in fibrin production were depicted. We simulated the correlation between MPs-ACT and standard plasma containing MPs prepared in vitro. The reproducibility of high-value and low-value samples was 6.0% and 10.8%, respectively. MPs-ACT sensitively detected hypercoagulable samples from patients with pre-eclampsia, hip fractures, and lung tumors. MPs-ACT largely reflects the procoagulant effect of MPs. MPs-ACT sensitively and rapidly detects hypercoagulability with MPs-rich plasma. It may be promising for the diagnosis of hypercoagulable states induced by MPs.

Is Patient-Specific Instrumentation Accurate and Necessary for Open-Wedge High Tibial Osteotomy? A Meta-Analysis.

The purpose of this meta-analysis was to identify if patient-specific instrumentation (PSI) could increase the accuracy of the correction in high tibial osteotomy (HTO) and to explore the assessment indices and the necessity of using a PSI in HTO. A systematic search was carried out using online databases. A total of 466 patients were included in 11 papers that matched the inclusion criteria. To evaluate the accuracy of PSI-assisted HTO, the weight bearing line ratio (WBL%), hip-knee-ankle angle (HKA), mechanical medial proximal tibial angle (mMPTA), and posterior tibial slope angle (PTSA) were measured preoperatively and postoperatively and compared to the designed target values. Statistical analysis was performed after strict data extraction with Review Manager (version 5.4). Significant differences were detected in WBL% (MD = -36.41; 95% CI: -42.30 to -30.53; p < 0.00001), HKA (MD = -9.95; 95% CI: -11.65 to -8.25; p < 0.00001), and mMPTA (MD = -8.40; 95% CI:-10.27 to -6.53; p < 0.00001) but not in PTSA (MD = 0.34; 95% CI: -0.59 to 1.27; p = 0.47) between preoperative and postoperative measurements. There was no significant difference between the designed target values and the postoperative correction values of HKA (MD = 0.14; 95% CI: -0.19 to 0.47; p = 0.41) or mMPTA (MD = 0.11; 95% CI -0.34 to 0.55; p = 0.64). The data show that 3D-based planning of PSI for HTO is both accurate and safe. WBL%, HKA, and mMPTA were the optimal evaluation indicators of coronal plane correction. Sagittal correction is best evaluated by the PTSA. The present study reports that PSI is accurate but not necessary in typical HTO.

The Optimal Therapy after Progression on Immune Checkpoint Inhibitors in MSI Metastatic Gastrointestinal Cancer Patients: A Multicenter Retrospective Cohort Study.

BACKGROUND: In microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers, the optimum therapy after the progression of immune checkpoint inhibitors (ICIs) is yet unknown. Here, we compared the efficacy of programmed death 1 (PD1)/programmed death ligand-1 (PD-L1) inhibitors plus other therapy and chemotherapy with or without targeted therapy in MSI/dMMR gastrointestinal cancer patients after progression on anti-PD1/PD-L1 monotherapy. METHODS: We retrospectively recruited MSI/dMMR gastrointestinal cancer patients who had progressed on anti-PD1/PD-L1 monotherapy. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and PFS ratio (PFSr) were compared between patients who received anti-PD1/PD-L1 plus other therapy (ICI-plus group) and patients who received chemotherapy with or without targeted therapy (chemo-targeted group). RESULTS: In total, 26 and 25 patients were recruited in the ICI-plus group and chemo-targeted group, respectively. Significantly better DCR (80.8% vs. 44.0%, p = 0.007), PFS (median PFS 6.9 months vs. 3.0 months, p = 0.001), OS (median OS NR vs. 14.1 months, p = 0.043), and PFSr (2.4 vs. 0.9, p = 0.021), along with a numerically higher ORR (23.1% vs. 12.0%, p = 0.503) were observed in the ICI-plus group compared with the chemo-targeted group. Multivariate analyses identified the therapy regimen as an important prognostic factor in gastrointestinal cancers. CONCLUSIONS: Compared to conventional chemotherapy with or without targeted therapy, continuing anti-PD1/PD-L1 in combination with other treatments showed better clinical outcomes in MSI/dMMR gastrointestinal cancer patients who progressed on PD1/PD-L1 blockade, which should be validated prospectively in clinical trials.

Defensing against oxidative stress in Caenorhabditis elegans of a polysaccharide LFP-05S from Lycii fructus.

Oxidative stress is closely associated with the initiation and progression of aging. Considerable interest centers in the potential application of natural polysaccharides in oxidative stress alleviation and senescence delay. Herein, LFP-05S, an acidic heteropolysaccharide from Lycii fructus, was purified and structurally characterized based on a combination strategy of molecular weight (MW) distribution, monosaccharide composition, methylation and NMR spectroscopy analysis. The dominant population of LFP-05S was composed of long homogalacturonan (HG) backbone interspersed with alternating sequences of intra-rhamnogalacturonans-I (RG-I) domains and branched arabinogalactan and arabinan. Orally supplied LFP-05S exhibited defensive modulation in paraquat (PQ)-damaged oxidative stress Caenorhabditis elegans by strengthening the internal defense systems. Under normal conditions, LFP-05S extended the lifespan without significant impairment of propagation. Overall, these results suggested LFP-05S and L. fructus are worth further exploration as promising redox-based candidates for the prevention and management of aging and related disorders.

Identification of Hub Genes and Pathways Associated with Oxidative Stress of Cartilage in Osteonecrosis of Femoral Head Using Bioinformatics Analysis.

OBJECTIVE: This study aimed to identify the hub genes and pathways of genes related to oxidative stress of cartilage in osteonecrosis of femoral head (ONFH), and to predict the transcription factors of the hub genes. METHODS: The GSE74089 was obtained from the Gene Expression Omnibus (GEO) database, including 4 necrotic tissues and 4 normal tissues, and the differentially expressed genes (DEGs) were identified by limma package in R language. Simultaneously, we searched for the genes related to oxidative stress in the Gene Ontology (GO) database. GO and signaling pathways analysis were performed using DAVID, Metascape, and GSEA. Protein-protein interaction (PPI) network was constructed using the STRING database, and the Degree algorithm of Cytoscape software was used to screen for hub genes. Finally, the NetworkAnalyst web tool was used to find the hub genes' transcriptional factors (TFs). RESULTS: In total, 440 oxidative stress-related genes were found in GSE74089 and GO database, and 88 of them were significantly differentially expressed. These genes were mainly involved in several signaling pathways, such as MAPK signaling pathway, PI3K-AKT-mTOR signaling pathway, FOXO signaling pathway. The top 10 hub genes were JUN, FOXO3, CASP3, JAK2, RELA, EZH2, ABL1, PTGS2, FBXW7, MCL1. Besides, TFAP2A, GATA2, SP1, and E2F1 may be the key regulatory factors of hub genes. CONCLUSIONS: We identified some hub genes and signaling pathways associated with oxidative stress in ONFH through a series of bioinformatics analyses.

Mapping knowledge landscapes and emerging trends of the links between osteoarthritis and osteoporosis: A bibliometric analysis.

Background: Osteoarthritis has the characteristics of degenerative changes in articular cartilage and secondary osteoporosis, and it is a common chronic irreversible joint disease. In addition to affecting articular cartilage, subchondral bone, joint capsule and synovial membrane also undergo pathological changes during the development of the disease. Multiple studies have revealed that patients with osteoarthritis were found to have a significantly increased risk of osteoporosis, which also contributes to the progression of osteoarthritis. However, in the current existing studies, we found that no scholars have used bibliometric analysis in the study of the relationship between osteoarthritis and osteoporosis. From the perspective of bibliometrics, this study summarizes in detail the degree of cooperation between countries, research institutions, authors, and related journals in the field of osteoarthritis and osteoporosis research and their respective influence. In this way, the evolution of knowledge structure, the change of research focus and the hot topics with research potential in the future can be further visualized and analyzed. Methods: Search the Web of Science core collection in Science Citation Index Expanded for articles and reviews of research on osteoarthritis and osteoporosis from 1998 to 2021. Bibliometric tools such as VOSviewer, CiteSpace, were be frequently used in our study. They are mainly used to analyze collaborations between countries, research institutions, and publication authors. Meantime, co-citation analysis of journals, co-occurrence analysis of keywords and subject categories will also be reflected in the study. Results: According to the search strategy, 1,078 publications were included during the period 1998-2021. And the number of annual publications on the relationship between osteoarthritis and osteoporosis is on the rise. The United States has achieved the most and contributed the most in this field and the Boston University was the most prolific institution. For the statistical analysis of published publications, Reginster JY had the highest number of publications, while Felson DT had the highest co-citation frequency. Respectively, Osteoarthritis And Cartilage was the most productive journal in this area of research. The keywords "inflammation," "expression," and "mesenchymal stem cells" may also be the development trend and research hotspot of the future research direction in this field. Conclusions: In our study, the relationship between osteoarthritis and osteoporosis was analyzed by using literature measurement. These analysis results can lead researchers to learn more directly about the trend in this area and provide guidance for determining popular research directions.

Circular RNA PLEC acts as a sponge of microRNA-198 to promote gastric carcinoma cell resistance to paclitaxel and tumorigenesis.

Gastric carcinoma (GC) is one of the most frequent types of malignancy worldwide. Resistance to paclitaxel (PTX) has become an obstacle to the prognosis of GC, and the underlying mechanism is not clear. A previous study identified GC-related circRNAs via microarray analysis and bioinformatics analysis, and we discovered that circPLEC (hsa_circ_104722) was markedly upregulated in GC tissues and cells. The molecular mechanism of circPLEC in PTX-resistant GC cells still needs to be explored. In the present study, qRT-PCR demonstrated that circPLEC was upregulated in PTX-resistant GC tissues and cells, indicating that circPLEC boosts the PTX resistance of GC. circPLEC downregulation weakened GC resistance to PTX and tumorigenesis, migration and invasion and promoted the apoptosis of PTX-resistant GC cells. MiR-198 inhibitor reversed the effect of circPLEC downreguAlation in PTX-resistant GC cells, and MUC19 downregulation weakened GC resistance to PTX and tumorigenesis and improved the apoptosis of PTX-resistant GC cells. In summary, circPLEC acts as a sponge of miR-198 to promote the PTX resistance and tumorigenesis of GC cells by regulating MUC19 expression.