Association Between Hashimoto's Thyroiditis and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study.

Background: We aim to investigate the possible causal association between Hashimoto's thyroiditis (HT) and rheumatoid arthritis (RA) using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted to evaluate the causal association between HT and RA. We obtained summary statistics data from two extensive genome-wide association studies (GWAS) comprising 15,654 cases of HT and 14,361 cases of RA. The primary effect estimate utilized in this study was the inverse-variance weighted (IVW) method. To ensure the reliability and stability of the results, we employed several additional methods for testing, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. Results: Our study revealed compelling evidence of bidirectional causality between HT and RA. When HT was considered as an exposure factor and RA was considered as an outcome factor, this study revealed a positive correlation between HT and RA (IVW: odds ratio [OR] = 2.4546, 95% confidence interval [CI], 1.1473-5.2512; p = 0.0207). Conversely, when we examined RA as the exposure factor and HT as the outcome factor, we still found a positive correlation between them (IVW: OR = 1.2113, 95% CI, 1.1248-1.3044; p = 3.9478 × 10-7). Conclusions: According to our research findings, there exists a bidirectional positive causal relationship between HT and RA among European populations. This implies that individuals with HT have an elevated risk of developing RA, and conversely, individuals with RA have an increased risk of developing HT.

The GDNF-gel/HA-Mg conduit promotes the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway.

Magnesium (Mg)-based conduits have gained more attention in repairing peripheral nerve defects. However, they are limited due to poor corrosion resistance and rapid degradation rate. To tackle this issue, glial cell line-derived neurotrophic factor (GDNF)- Gelatin methacryloyl (Gel)/hydroxylapatite (HA)-Mg nerve conduit was developed and implanted in sciatic nerve defect model in Sprague-Dawley (SD) rats. The sciatic functional index measurement showed that the GDNF-Gel/HA-Mg nerve conduit effectively promoted the recovery of sciatic nerve function. The pathological examination results showed that there were more regenerated nerve tissues in GDNF-Gel/HA-Mg group, with a higher number of regenerating axons, and the thickness of the myelin sheath was significantly larger than that of control group (NC group). Immunofluorescence results revealed that the GDNF-Gel/HA-Mg conduit significantly promoted the expression of genes associated with nerve repair. RNA-seq and molecular test results indicated that GDNF-Gel/HA-Mg might be involved in the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway. Biological sciences; Neuroscience; Molecular neuroscience; Techniques in neuroscience.

Metformin Treatment Reduces the Incidence of Rheumatoid Arthritis: A Two-Sample Mendelian Randomized Study.

Several studies have shown that rheumatologic patients can benefit from metformin, but it remains unclear whether metformin treatment is causally associated with the risk of rheumatoid arthritis (RA). A two-sample Mendelian randomization (MR) study was conducted to investigate the causal relationship between metformin treatment and the incidence of rheumatoid arthritis. The genome-wide significant (p < 5 × 10-8) single-nucleotide polymorphisms (SNPs) associated with metformin use were selected as instrumental variables (IVs). Summary statistics on RA were extracted from a large genome-wide association study (GWAS) meta-analysis. The inverse variance-weighted (IVW) method was used as the determinant of the causal effects of metformin treatment on RA. Cochran's Q was used to detect heterogeneity. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression were used to detect horizontal pleiotropy. A total of 34 SNPs significantly associated with metformin treatment were obtained. Thirty-two SNPs were selected as IVs after removing two SNPs for being palindromic with intermediate allele frequencies (rs11658063 and rs4930011). The IVW results showed a negative causal association between metformin treatment and RA (OR = 0.0232, 95% CI 1.6046 × 10-3 - 0.3368; p = 0.006). Meanwhile, no heterogeneity or pleiotropy was detected, indicating that the results were reliable. This study indicated a negative causality between metformin treatment and RA, indicating that the treatment of metformin can prevent the pathogenesis of RA.

The Burden of Rheumatoid Arthritis: Findings from the 2019 Global Burden of Diseases Study and Forecasts for 2030 by Bayesian Age-Period-Cohort Analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a key health issue worldwide. Due to early identification and effective treatment strategies, the disease pattern of RA has also changed. However, the most comprehensive and up-to-date information about the burden of RA and its trends in subsequent years is lacking. OBJECTIVE: this study aimed to report the global burden of RA by sex, age, region, and forecast for 2030. METHOD: Publicly available data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used in this study. The trends in the prevalence, incidence, and disability-adjusted life years (DALYs) of RA from 1990 to 2019 were reported. The global burden of RA in 2019 was reported by a sex, age, and sociodemographic index (SDI). Finally, the trends in the following years were predicted by Bayesian age-period-cohort (BAPC) models. RESULTS: Globally, the age-standardized prevalence rate increased from 207.46 (95% UI:189.99 to 226.95) in 1990 to 224.25 (95% UI: 204.94 to 245.99) in 2019, with an estimated annual percent change (EAPC) of 0.37% (95% CI: 0.32 to 0.42). Regarding the incidence, the age-standardized incidence rate (ASR) increased from 12.21 (95% UI: 11.13 to 13.38) to 13 (95% UI: 11.83 to 14.27) per 100,000 people from 1990 to 2019, with an EAPC of 0.3% (95% CI: 11.83 to 14.27). The age-standardized DALY rate also increased from 39.12 (95% UI: 30.13 to 48.56) per 100,000 people in 1990 to 39.57 (95% UI: 30.51 to 49.53) in 2019, with an EAPC of 0.12% (95% CI: 0.08% to 0.17%). There was no significant association between the SDI and ASR when the SDI was lower than 0.7, while there was a positive association between the SDI and ASR when the SDI was higher than 0.7 The BAPC analysis showed that the ASR was estimated to be up to 18.23 in females and approximately 8.34 per 100,000 people in males by 2030. CONCLUSION: RA is still a key public health issue worldwide. The global burden of RA has increased over the past decades and will continue to increase in the coming years, and much more attention should be given to early diagnosis and treatment to reduce the burden of RA.

Synovial fluid neutrophil extracellular traps could improve the diagnosis of periprosthetic joint infection.

AIMS: This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). METHODS: In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. RESULTS: The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. CONCLUSION: SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly.Cite this article: Bone Joint Res 2023;12(2):113-120.

Causal relationships between rheumatism and dyslipidemia: A two-sample Mendelian randomization study.

Background: Dyslipidemia is often observed in rheumatic diseases, such as ankylosing spondylitis (AS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), yet it remains to be detected whether rheumatic diseases have a causal effect on dyslipidemia. Methods: Significant (P < 5 × 10-8) and independent (r2 < 0.1) single-nucleotide polymorphisms in genome-wide association studies were selected as instrumental variables to conduct Mendelian randomization (MR) analysis. Inverse variance weighted, weighted median, and MR-Egger regression were adopted for the causal inference. Subsequently, sensitivity analysis was conducted to assess the stability and reliability of MR. Results: The MR results revealed positive causal relationships of AS with total cholesterol (TC) (ß = 0.089, 95% CI = 0.050 to 0.128, P = 6.07 × 10-6), low-density lipoprotein (LDL) (ß = 0.087, 95% CI = 0.047 to 0.127, P = 1.91 × 10-5), and high-density lipoprotein (HDL) (ß = 0.043, 95% CI = 0.001 to 0.074, P = 0.009). There was no causal effect of RA on TC (ß = 0.008, 95% CI = 4.86 × 10-4 to 0.017, P = 0.064), LDL (ß = 6.4 × 10-4, 95% CI = -0.008 to 0.007, P = 0.871), or HDL (ß = 0.005, 95% CI = -0.003 to 0.013, P = 0.200). Additionally, SLE had negative causal links for TC (ß = -0.025, 95% CI = -0.036 to -0.015, P = 4.42 × 10-6), LDL (ß = -0.015, 95% CI = -0.025 to -0.005, P = 0.003), and HDL (ß = -0.013, 95% CI = -0.021 to -0.004, P = 0.004). The results were stable and reliable. Conclusion: This study suggested positive causal effects of AS on TC, LDL, and HDL and negative causal effects of SLE on these cholesterol levels, which could provide much help for the pathogenesis and treatment of rheumatic disease patients with dyslipidemia.

The Causal Relationship Between Rheumatoid Arthritis and Mechanical Complications of Prosthesis After Arthroplasty: A Two-Sample Mendelian Randomization Study.

The causal effects of rheumatoid arthritis (RA) on complications of arthroplasty are yet to be established. This study was the first to explore the causal effect of RA on mechanical complications of prosthesis through two-sample Mendelian randomization (MR). In the MR analysis, RA was selected as the exposure in this study while single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) were selected as the instrumental variables (IVs). Summary statistics data on mechanical complications of prosthesis was extracted from publicly available GWAS data, including 463,010 European descent individuals. MR analysis was performed using the standard inverse variance weighted method (IVW). Furthermore, other methods (MR Egger, weighted median, simple mode, and weighted mode) were also done to verify the results. Finally, the sensitivity analysis was executed. Results of the standard IVW showed that RA possibly increases the risk of mechanical complications of prosthesis [OR = 1.000255; 95% CI = (1.0001035, 1.000406); p = 9.69 × 10 -4 ]. This outcome was also verified by other methods including weighted median [OR = 1.000285; 95% CI = (1.0001032, 1.000466); p = 1.41 × 10-3], simple mode [OR = 1.000446; 95% CI = (1.0001116, 1.000781); p = 1.04 × 10-2], and weighted mode [OR = 1.000285; 95% CI = (1.0001032, 1.000466); p = 2.29 × 10-3]. No heterogeneity and directional pleiotropy was observed upon sensitivity analysis, indicating the stability and reliability of the result. In summary, the present study showed that RA potentially increases the risks of complications of prosthesis, which might provide guidance in arthroplasty on RA patients.

Preparation of ultra-high mechanical strength wear-resistant carbon fiber textiles with a PVA/PEG coating.

Polyvinyl alcohol (PVA) is an organic polymer that is non-toxic, harmless to the human body, and has good biocompatibility. Polyethylene glycol (PEG) is a polymer that has good lubricity and compatibility. The unique graphite structure of carbon fibers can promote the potential application of carbon-fiber composites in tribology. This study explores the relationship between two kinds of organic polymer compounds and carbon fiber cloth (CFC), specifically a PVA/PEG composite coating that is impregnated on the CFC surface. The CFC is synthesized by chemical cross-linking, and the CFC composites (PVA/PEG/CFC) were synthesized. The tribological properties of PVA/PEG/CFC were tested under different concentrations, loads, and velocities. The effects of the different lubricants, surface morphologies, and tensile strengths on the mechanical and tribological properties of PVA/PEG/CFC were studied. In comparison to the original CFC, the friction coefficient and wear morphology of the composite material were reduced and the friction coefficient trend was stable. The addition of PVA/PEG improved the surface lubrication performance of the composite material and reduced the average friction coefficient. In addition, under the different lubrication mechanisms, oil as a lubricant can significantly reduce the friction coefficient and surface wear. In summary, the biocompatible coating process that is proposed in this study can effectively improve the tribological properties of the surface of the CFC.

Causal Relationships Between Osteoarthritis and Senile Central Nerve System Dysfunction: A Bidirectional Two-Sample Mendelian Randomization Study.

Background: The relationship between osteoarthritis (OA) and senile central nervous system dysfunctions (CNSDs), including Parkinson's disease (PD), Alzheimer's disease (AD), and ischemic stroke (IS) has gradually attracted attention. At present, the causal relationship between OA and CNSD remains unclear. The aim of this study was to assess the causal effects of CNSD and OA using Mendelian randomization (MR). Methods: Genome-wide association study summary data for CNSD and OA were obtained. Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), and significant (P < 5.0 × 10-8) and independent (r 2 < 0.1) SNPs were extracted for bidirectional MR analysis. Inverse variance weighted (IVW) was used to assess these causal relationships. The results are reported as odds ratios (ORs). Subsequently, heterogeneity was tested using the Cochran's Q test, pleiotropy was tested using the MR-Egger intercept, and sensitivity analysis was performed using the leave-one-out sensitivity test. Results: The MR results of the causal relationship between PD and OA showed that there was a positive causal effect of OA on PD, which was estimated by IVW (OR = 1.194, 95%CI = 1.036, 1.378; P = 0.0144). Moreover, the MR analysis by IVW also showed that IS had a positive effect on OA (OR = 1.033, 95%CI = 1.002, 1.066; P = 0.0355). These results are reliable and stable, as confirmed by sensitivity tests. Conclusion: This study showed a positive causal effect of OA on PD, but there was a null effect of OA on AD and OA on IS.

The Relationship Between Body Mass Index and Bone Mineral Density: A Mendelian Randomization Study.

Body mass index (BMI) is closely associated with bone mineral density (BMD) in both men and women. However, the relationship between BMI and BMD varies according to different studies. Using SNPs strongly associated with BMI in 336,107 individuals, we conducted a two-sample Mendelian randomization study to identify whether and to what extent BMD at different skeletal sites was affected by BMI. A power calculation was also performed. We found that BMI may causally increase lumbar BMD (ß 0.087; 95% CI 0.025 to 0.149; P = 0.006) and heel calcaneus BMD (ß 0.120; 95% CI 0.082 to 0.157; P = 1 × 10-7). The associations of BMI with forearm and femoral neck BMD were not statistically significant. Our study suggested that higher BMI plays a causal role in increasing BMD and the effects are similar across the skeleton. BMI was causally and positively associated with lumbar and heel calcaneus BMD. However, no statistically significant effects were observed for BMI on femoral neck or forearm BMD.

Fluid shear stress induces Runx-2 expression via upregulation of PIEZO1 in MC3T3-E1 cells.

Mechanically induced biological responses in bone cells involve a complex biophysical process. Although various mechanosensors have been identified, the precise mechanotransduction pathway remains poorly understood. PIEZO1 is a newly discovered mechanically activated ion channel in bone cells. This study aimed to explore the involvement of PIEZO1 in mechanical loading (fluid shear stress)-induced signaling cascades that control osteogenesis. The results showed that fluid shear stress increased PIEZO1 expression in MC3T3-E1 cells. The fluid shear stress elicited the key osteoblastic gene Runx-2 expression; however, PIEZO1 silencing using small interference RNA blocked these effects. The AKT/GSK-3ß/ß-catenin pathway was activated in this process. PIEZO1 silencing impaired mechanically induced activation of the AKT/GSK-3ß/ß-catenin pathway. Therefore, the results demonstrated that MC3T3-E1 osteoblasts required PIEZO1 to adapt to the external mechanical fluid shear stress, thereby inducing osteoblastic Runx-2 gene expression, partly through the AKT/GSK-3ß/ß-catenin pathway.

Identification of Hub Genes in Duchenne Muscular Dystrophy: Evidence from Bioinformatic Analysis.

The hub genes and signaling pathways associated with Duchenne muscular dystrophy (DMD) were predicted by bioinformatic methods to improve the therapeutic effect and quality of life of patients. Microarray data sets GSE465, GSE1004, and GSE1007 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by GEO2R, and function enrichment analyses were performed by DAVID. The protein-protein interaction (PPI) network was constructed and the module analysis was performed using STRING and Cytoscape. A total of 195 DEGs were identified. The enriched functions and pathways of the DEGs include extracellular exosome, focal adhesion, extracellular matrix (ECM), focal adhesion, PI3K-Akt signaling pathway, calcium signaling pathway, and ECM-receptor interaction. Fifteen hub genes were identified. DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the pathogenesis and progression of DMD, and provide candidate targets for treatment of DMD.

Slow-release lubrication effect of graphene oxide/poly(ethylene glycol) wrapped in chitosan/sodium glycerophosphate hydrogel applied on artificial joints.

The artificial joints would go through serious wear after implantation surgery due to the poor lubrication of the body fluid, and the biomimetic lubricants directly injected in vitro is easy to be absorbed by human tissues, and after a period of time, it will lose its lubrication effect. However, the composite hydrogel with slow-release lubrication effect provides a new way for the lubrication of artificial joints. In this study, Graphene oxide/Poly(ethylene glycol) (GO/PEG) composites were prepared to improve the artificial joint lubrication, and through wrapped in the Chitosan/Sodium glycerophosphate (CS/GP) hydrogel, the GO/PEG lubricant will be released under the squeezing action, thus to prolong the service time of biomimetic lubricants. The friction experimental results showed that GO/PEG had better lubrication effect, and the average friction coefficient of the slow-release solution was below 0.03, especially with the pressure increasing. GO, PEG and small molecule GP in the slow-release solution through hydrogen-bond interaction might form a particular structure, which led to the good lubricating effect. The experiments of cell and acute toxicity in vivo showed that GO and its composite hydrogel had good biocompatibility.

Carbon dots intensified poly (ethylene glycol)/chitosan/sodium glycerophosphate hydrogel as artificial synovium tissue with slow-release lubricant.

The ultra-high molecular weight polyethylene (UHMWPE) and metal artificial joint pair is limited by wear debris and short service life. Here we report the development of a hydrogel which exhibits lubricant release to intensify the lubrication effect of artificial joints.This study adopted an injectable method to prepare carbon dots/poly (ethylene glycol)/chitosan/sodium glycerophosphate (CDs/PEG/CS/GP) composite hydrogel, and the carbon dots were used to intensify the rheological and mechanical properties. In addition, the composite hydrogel had slow-release properties, and the release solution contained CDs, PEG and GP has excellent lubrication effect. At last, the MTT assay, LIVE/DEAD staining, H&E staining results and safety evaluation in BALC/c mice proved that the hydrogels had good biocompatibilility and were safety for application in vivo.

Effects of periarticular injection on analgesic effects and NSAID use in total knee arthroplasty and total hip arthroplasty

OBJECTIVES: This study examined periarticular multimodal drug injection and the use of nonsteroidal anti-inflammatory drugs for an early analgesic effect after total knee arthroplasty and total hip arthroplasty. Patient satisfaction and benefits from the treatment were also assessed. METHODS: A total of 110 patients who were scheduled to undergo total knee arthroplasty and 86 patients who were scheduled to undergo total hip arthroplasty were divided into two groups, the study group and the control group. The study group received a periarticular multimodal drug injection during surgery. The control group received an equal volume of normal saline. All patients received an analgesia pump and a moderate dose of nonsteroidal anti-inflammatory drugs. Resting and motion Numeric Rating Scale scores, the Western Ontario and McMaster Universities Arthritis Index, knee or hip joint range of motion, length of postoperative hospital stay, patient satisfaction, total nonsteroidal anti-inflammatory drug consumption and side effects were recorded. RESULTS: Both study groups exhibited significant improvement in pain Numeric Rating Scale scores during rest and exercise several days after the surgery. The range of joint motion was greater in the study group, and the length of postoperative hospital stay was shorter than that in the control group. Patients in the study group consumed fewer nonsteroidal anti-inflammatory drugs and reported greater satisfaction with surgery. CONCLUSION: Intraoperative periarticular multimodal drug injection significantly relieved pain after surgery and reduced nonsteroidal anti-inflammatory drug consumption. These patient had a better postoperative experience, including satisfaction and rehabilitation.

Effects of periarticular injection on analgesic effects and NSAID use in total knee arthroplasty and total hip arthroplasty.

OBJECTIVES: This study examined periarticular multimodal drug injection and the use of nonsteroidal anti-inflammatory drugs for an early analgesic effect after total knee arthroplasty and total hip arthroplasty. Patient satisfaction and benefits from the treatment were also assessed. METHODS: A total of 110 patients who were scheduled to undergo total knee arthroplasty and 86 patients who were scheduled to undergo total hip arthroplasty were divided into two groups, the study group and the control group. The study group received a periarticular multimodal drug injection during surgery. The control group received an equal volume of normal saline. All patients received an analgesia pump and a moderate dose of nonsteroidal anti-inflammatory drugs. Resting and motion Numeric Rating Scale scores, the Western Ontario and McMaster Universities Arthritis Index, knee or hip joint range of motion, length of postoperative hospital stay, patient satisfaction, total nonsteroidal anti-inflammatory drug consumption and side effects were recorded. RESULTS: Both study groups exhibited significant improvement in pain Numeric Rating Scale scores during rest and exercise several days after the surgery. The range of joint motion was greater in the study group, and the length of postoperative hospital stay was shorter than that in the control group. Patients in the study group consumed fewer nonsteroidal anti-inflammatory drugs and reported greater satisfaction with surgery. CONCLUSION: Intraoperative periarticular multimodal drug injection significantly relieved pain after surgery and reduced nonsteroidal anti-inflammatory drug consumption. These patient had a better postoperative experience, including satisfaction and rehabilitation.