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.

MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5.

BACKGROUND: Proteasome inhibition is a promising strategy for cancer therapy. Bortezomib, which primarily targets the chymotrypsin-like activity of PSMB5, has demonstrated efficacy in various tumors. However, there is variable sensitivity to bortezomib, which could be attributed, in part, to variations in the expression of proteasome subunits. METHODS AND RESULTS: In this study, we investigated whether miR-383 affects the expression of proteasome subunits in osteosarcoma (OS) cells, and if so, whether OS cells display differential sensitivity to bortezomib concerning miR-383 expression. We detected a decreased miR-383 expression in OS cells and tissues. Then we found a negative correlation between the cytotoxicity of bortezomib and the expression level of the proteasome 20S core particle subunit ß5 (PSMB5). Intriguingly, we identified PSMB5 as a direct target of miR-383. Increased expression of miR-383 resulted in decreased PSMB5 expression and increased sensitivity to bortezomib in OS cells. CONCLUSIONS: In summary, our findings present the initial comprehensive analysis of the function of miR-383 in OS. The outcomes indicate that miR-383 may augment the anticancer effect of bortezomib through PSMB5 repression, offering a novel therapeutic approach in OS and a fresh pathway for proteasome regulation.

Prevalence and Risk Factors of Osteoporosis in a Chinese Population: A Cross-Sectional Study in Xi'an, Shaanxi Province, China.

BACKGROUND Osteoporosis is a systemic chronic disease characterized by bone mineral density (BMD) reduction. This study aimed to assess the prevalence of osteoporosis and fracture risks in northwestern China and investigate the related anthropometric risk factors. MATERIAL AND METHODS Between July 2022 and August 2022, 1429 participants (1295 females, 134 males) with measured BMD were recruited to participate in this cross-sectional study. Data on height, weight, and T score were collected. Spearman's correlation and multiple linear regression analysis were used to investigate the relationships between various demographic factors and BMD and the 10-year risk of major osteoporotic fracture (MO) and hip fracture (HP). RESULTS The overall prevalence of osteoporosis in northwest China was 42.34%, with 44.56% in females and 20.90% in males. Age negatively affects females' T scores (r=-0.304, P<0.05), and height positively influences both sexes' T scores (r=0.059 P<0.05). Age (r=0.148, P<0.05) and height were positive predictors of MO (r=0.027, P<0.05), while weight was a negative predictor (r=-0.035, P<0.05). The conclusion for HP was consistent with that of MO, except for the T score, which was a positive predictor of HP (r=0.014, P<0.05). CONCLUSIONS The prevalence of osteoporosis in northeast China is high. The association between anthropometric parameters and osteoporosis in adults in northwest China is different between sexes.

Rheumatoid arthritis and gastroesophageal reflux disease: a bidirectional and multivariable two-sample Mendelian randomization study.

Aims/hypothesis: The association between gastroesophageal reflux disease (GERD) and rheumatoid arthritis (RA) has been reported by many observational studies in the Asian population. This study aimed to examine the bidirectional causal effects between GERD and RA by two-sample Mendelian randomization (MR) analyses using genetic evidence. Methods: Two-sample Mendelian randomization analyses were performed to determine the causal effect of GERD (129,080 cases vs. 602,604 control participants) on RA (6,236 cases vs. 147,221 control participants) and RA on GERD, respectively. The inverse-variance weighted (IVW) method was used as the primary analysis. Weighted median and MR-Egger regression were taken as supplementary analyses. Cochran's Q test evaluated the heterogeneity. Horizontal pleiotropy was detected by estimating the intercept term of MR-Egger regression. Furthermore, multivariable MR analyses were performed to exclude the influence of confounding factors, including the years of schooling, BMI, and time spent watching television, between GERD and RA. Result: Both univariate MR (UVMR) and multivariable MR (MVMR) provided valid evidence that RA was causally and positively influenced by GERD (UVMR: OR = 1.49, 95% CI = 1.25-1.76, p = 6.18*10-6; MVMR: OR = 1.69, 95% CI = 1.24-2.31, p = 8.62*10-4), whereas GERD was not influenced by RA (UVMR: OR = 1.03, 95% CI = 1.00-1.06, p = 0.042; MVMR: OR = 1.04, 95% CI = 1.00-1.07, p = 0.0271). Conclusion: Our comprehensive bidirectional MR analysis found that for the European population, GERD can induce the occurrence of RA (OR = 1.69, p < 0.00125), whereas RA only has no significant influence on GERD. In particular, patients with GERD are suffering a 69% increased risk of RA occurrence, which means GERD is a substantial risk factor for RA.

Changes in Anxiety and Depression After THA in Patients with Ankylosing Spondylitis and the Affecting Factors.

Objective: Hip ankylosis is a prevalent condition in patients with Ankylosing spondylitis (AS) that can significantly impact their psychological well-being. This study aimed to investigate the impact of Total Hip Arthroplasty (THA) on anxiety and depression among AS patients. Methods: 62 AS patients undergoing primary THA were recruited and separated into two groups based on preoperative hip motion. The 40 patients with hip mobility of 0° were assigned to group A, and others were assigned to group NA. Self-rating Anxiety Scale (SAS), Self-rating Depression scale (SDS), Harris hip scores (HHS) and 36-Item Short Form Survey (SF-36) were obtained one week before and there, six and twelve months after THA. Results: The study found that AS patients in group A had significantly higher levels of anxiety and depression (SAS score = 75.05±2.79, SDS index score = 0.74±0.02) compared to group B (SAS score = 54.58±3.35, SDS index score= 0.64±0.03, P=0.01). However, both groups showed significant improvements in anxiety and depression scores from there to twelve months after THA (P<0.001). Correlation analyses revealed that the improvement in group NA was associated with hip pain relief (p<0.001), while the improvement in group A was related to joint function, disease duration, age at THA and spine imaging lesions (p<0.001). Conclusion: Some degree of anxiety and depression was present in both groups of AS patients. Levels of depression and anxiety were higher in patients with combined hip ankylosis. And their improvement was associated with improved hip function and quality of life after THA. Hip pain relief played a significant role in patients without hip joint ankylosis. The impact of the degree of lesion on spinal imaging on psychological status needs to be considered in both groups.

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.

Total Hip Arthroplasty in Patients with Crowe III/IV Developmental Dysplasia of the Hip: Acetabular Morphology and Reconstruction Techniques.

The severe anatomic deformities render acetabular reconstruction as one of the greatest challenges in total hip arthroplasty (THA) for patients with Crowe III/IV developmental dysplasia of the hip (DDH). Thorough understanding of acetabular morphology and bone defect is the basis of acetabular reconstruction techniques. Researchers have proposed either true acetabulum position reconstruction or high hip center (HHC) position reconstruction. The former can obtain the optimal hip biomechanics, including bulk femoral head autograft, acetabular medial wall displacement osteotomy, and acetabular component medialization, while the latter is relatively easy for hip reduction, as it can avoid neurovascular lesions and obtain more bone coverage; however, it cannot achieve good hip biomechanics. Both techniques have their own advantages and disadvantages. Although there is no consensus on which approach is better, most researchers suggest the true acetabulum position reconstruction. Based on the various acetabular deformities in DDH patients, evaluation of acetabular morphology, bone defect, and bone stock using the 3D image and acetabular component simulation techniques, as well as the soft tissue tension around the hip joint, individualized acetabular reconstruction plans can be formulated and appropriate techniques can be selected to acquire desired clinical outcomes.

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.

SIX4 upregulates IDH1 and metabolic reprogramming to promote osteosarcoma progression.

Metabolism reprogramming plays an important role in tumorigenesis and osteosarcoma metastasis. Sine oculis homeobox 4 (SIX4) is reported to be a key transcription factor that is involved in glycolysis reprogramming of cancer cells. However, the role of SIX4 in osteosarcoma progression remains unknown. The expression profile of SIX4 in OS was evaluated in surgery samples of osteosarcoma patients. Functional studies were performed in vitro and in vivo. We found that SIX4 is significantly overexpressed in osteosarcoma and related to the undesirable prognosis of osteosarcoma patients. SIX4 promotes progression of osteosarcoma via upregulating isocitrate dehydrogenase 1 (IDH1), which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.

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.

Nuclear receptor coactivator 3 transactivates proinflammatory cytokines in collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system mistakenly attacks joints. The molecular mechanisms underlying RA pathology are still under investigation. In this study, we discovered overexpression of nuclear receptor coactivator 3 (NCOA3) in the joint tissues of type II collagen-induced arthritis (CIA) mice, an important autoimmune model of human RA. Administration of two NCOA3 inhibitors, gossypol (GSP) and SI-2 hydrochloride (SHC), significantly alleviated inflammation and improved the outcomes of CIA mice. In vivo and in vitro experiments revealed that NCOA3 assembled a transcriptional complex with a histone acetyltransferase p300 and two subunits of nuclear factor kappa B (NF-κB). This complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Knockdown of NCOA3 or in vitro treatments with GSP and SHC impaired the assembly of NCOA3-p300-NF-κB complex and decreased the expression of proinflammatory cytokine genes. Taken together, our results demonstrated that NCOA3 acts as a mediator of proinflammatory cytokine genes in CIA mice and that inhibition of the NCOA3-p300-NF-κB complex may represent a new avenue for improving RA outcomes.

Addition of Tibial Tubercle Osteotomy to Combined MPFL Reconstruction and Lateral Retinacular Release not Recommended for Recurrent Patellar Dislocation in Patients with 15 to 20 mm TT-TG.

Surgery is the primary treatment for recurrent patellar dislocation. However, there is still a lack of consensus regarding the choice of combined surgical methods due to the complexity of the anatomical factors. This study aimed to investigate the efficacy and radiological changes in medial patellofemoral ligament reconstruction (MPFLR) and lateral retinacular release (LRR) with and without tibial tubercle osteotomy (TTO) for recurrent patellar dislocation in patients with a tibial tubercle-trochlear groove (TT-TG) distance of 15 to 20 mm. Fifty-four patients were enrolled in this retrospective study between 2010 and 2014. The average patient age was 21.6 ± 5.0 years. All patients underwent MPFLR and LRR, and in 18 patients, these procedures were combined with TTO. Patients were evaluated preoperatively and postoperatively for patellar lateral shift, patellar tilt angle, TT-TG distance, Q-angle, Caton-Deschamps index (CDI), Kujala, and Lysholm scores. The minimally clinical important difference was used to compare clinical outcomes between two groups. In the mean follow-up of 82.6 ± 15.9 months, functional scores improved significantly in both groups (p < 0.01). There were no significant differences in postoperative function scores between the two groups (Kujala, p = 0.25, mean difference = 1.5, 95% confidence interval [CI]: -1.4-4.4; Lysholm, p = 0.76, mean difference = -0.6, 95% CI: -5.9-4.7). Additionally, TTO significantly decreased Q-angle (23.6 ± 2.4 vs. 17.4 ± 2.9, p < 0.01), TT-TG (17.1 ± 1.5 vs. 10.4 ± 1.8, p < 0.01), and CDI (1.18 ± 0.12 vs. 1.08 ± 0.07, p < 0.01). Combined MPFLR and LRR with and without TTO are both effective techniques for recurrent patellar dislocation. Additional osteotomy can correct patellar alta and tibial tubercle lateralization. However, given that there were no significant differences in postoperative functional scores or recurrence rate between groups, we may not recommend TTO in addition to MPFLR and LRR in patients with TT-TG of 15 to 20 mm. Long-term and prospective cohort studies are required to assess further outcomes.

Causal associations of hand grip strength with bone mineral density and fracture risk: A mendelian randomization study.

Background: Muscle strength has been shown to exert positive effects on bone health. The causal relationship between hand grip strength and osteoporosis is an important public health issue but is not fully revealed. The goal of this study was to investigate whether and to what extent hand grip strength affects bone mineral density (BMD) and fracture risk. Methods: We conducted a state-of-the-art two-sample Mendelian randomization analysis. Genomewide significant (P<5×10-8) single nucleotide polymorphisms associated with hand grip strength were obtained. Summary level data of BMD and fractures at different body sites (lumbar spine, heel, forearm and femoral neck) was obtained from a large-scale osteoporosis database. The inverse variance weighted method was the primary method used for analysis, and the weighted-median, MR-Egger were utilized for sensitivity analyses. Results: The results provided strong evidence that hand grip strength trait was causally and positively associated with lumbar spine BMD (ß: 0.288, 95% CI: 0.079 to 0.497; P=0.007), while no causal relationship was found between hand grip strength and BMD at heel (ß: -0.081, 95% CI: -0.232 to 0.070; P=0.295), forearm (ß: 0.-0.101, 95% CI: -0.451 to 0.248; P=0.571) or femoral neck (ß: 0.054, 95% CI: -0.171 to 0.278; P=0.639). In addition, no statistically significant effects were observed for hand grip strength on fracture risks (ß: -0.004, 95% CI: -0.019 to 0.012; P=0.662). Conclusions: This study showed a positive causal relationship between hand grip strength and lumbar BMD, which is the most common site of osteoporotic fracture, but did not find a causal relationship between hand grip strength and BMD of heel, forearm, or femoral neck. No statistically significant effect of hand grip strength on fracture risk was observed. This study indicates variations in the abilities of hand grip strength trait to causally influence BMD at different skeleton sites. These results should be considered in further studies and public health measures on osteoporosis prevention strategies.

Exosomes derived from M2 macrophages induce angiogenesis to promote wound healing.

There is an urgent clinical need for an appropriate method to shorten skin healing time. Among most factors related to wound healing, M2 macrophages will be recruited to the wound area and play a pivotal role in a time-limiting factor, angiogenesis. The exploration of exosomes derived from M2 in angiogenesis promotion is an attractive research field. In this project, we found that exosomes from M2 (M2-EXO) promoted the angiogenic ability of HUVECs in vitro. With a series of characteristic experiments, we demonstrated that M2-EXO inhibited PTEN expression in HUVECs by transferring miR-21, and further activated AKT/mTOR pathway. Then, using a full-thickness cutaneous wound mice model, we demonstrated that M2-EXO could be used as a promotor of angiogenesis and regeneration in vivo. Furthermore, M2-EXO-treated skin wounds exhibited regeneration of functional microstructures. These results demonstrate that M2-EXO can be used as a promising nanomedicine strategy for therapeutic exploration of skin healing with the potential to be translated into clinical practice.

Melatonin Attenuates Spinal Cord Injury in Mice by Activating the Nrf2/ARE Signaling Pathway to Inhibit the NLRP3 Inflammasome.

BACKGROUND: Spinal cord injury (SCI) is a central nervous system (CNS) trauma involving inflammation and oxidative stress, which play important roles in this trauma's pathogenesis. Therefore, controlling inflammation is an effective strategy for SCI treatment. As a hormone, melatonin is capable of producing antioxidation and anti-inflammation effects. In the meantime, it also causes a neuroprotective effect in various neurological diseases. Nrf2/ARE/NLRP3 is a well-known pathway in anti-inflammation and antioxidation, and Nrf2 can be positively regulated by melatonin. However, how melatonin regulates inflammation during SCI is poorly explored. Therefore, it was investigated in this study whether melatonin can inhibit the NLRP3 inflammasome through the Nrf2/ARE signaling pathway in a mouse SCI model. METHODS: A model of SCI was established in C57BL/6 mice and PC12 cells. The motor function of mice was detected by performing an open field test, and Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling were carried out to evaluate the survival of neurons. Mitochondrial dysfunction was detected by transmission electron microscopy (TEM) and by assessing the mitochondrial membrane potential. In addition, the expression of NLRP3 inflammasome and oxidative-stress-related proteins were detected through Western blot and immunofluorescence double staining. RESULTS: By inhibiting neuroinflammation and reducing neuronal death, melatonin promotes the recovery of neuromotor function. Besides this, melatonin is able to reduce the damage that causes neuronal mitochondrial dysfunction, reduce the level of reactive oxygen species (ROS) and malondialdehyde, and enhance the activity of superoxide dismutase and the production of glutathione peroxidase. Mechanically, melatonin inhibits the activation of NLRP3 inflammasomes and reduces the secretion of pro-inflammatory factors through the Nrf2/ARE signaling. CONCLUSIONS: In conclusion, melatonin inhibits the NLRP3 inflammasome through stimulation of the Nrf2/ARE pathway, thereby suppressing neuroinflammation, reducing mitochondrial dysfunction, and improving the recovery of nerve function after SCI.

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.

Coronal and sagittal spinopelvic alignment in the patients with unilateral developmental dysplasia of the hip: a prospective study.

BACKGROUND: How the hip dysplasia affects the spinopelvic alignment in developmental dysplasia of the hip (DDH) patients is unclear, but it is an essential part for the management of this disease. This study aimed to investigate the coronal and sagittal spinopelvic alignment and the correlations between the spinopelvic parameters and the extent of hip dysplasia or the low back pain in unilateral DDH patients. METHODS: From September 2016 to March 2021, 22 unilateral patients were enrolled in the DDH group with an average age of 43.6 years and 20 recruited healthy volunteers were assigned to the control group with an average age of 41.4 years. The Cobb angle, seventh cervical vertebra plumbline-central sacral vertical line (C7PL-CSVL), third lumbar vertebra inclination angle (L3IA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK) and lumbar lordosis (LL) were measured on the standing anteroposterior and lateral full-length standing spine radiographs. Additionally, the Oswestry Disability Index (ODI) and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were used to assess the degree of low back pain. RESULTS: Cobb angle (8.68 ± 6.21° vs. 2.31 ± 0.12°), L3IA (4.80 ± 5.47° vs. 0.83 ± 0.51°), C7PL-CSVL (1.65 ± 1.57 cm vs. 0.48 ± 0.33 cm), PT (15.02 ± 9.55° vs. 9.99 ± 2.97°) and TLK (7.69 ± 6.66° vs. 3.54 ± 1.63°) were significantly larger in DDH patients, whereas LL (37.41 ± 17.17° vs. 48.79 ± 7.75°) was significantly smaller (P < 0.05). No correlation was found between significantly different spinopelvic parameters and the extent of dysplasia. Statistical analysis revealed correlations between ODI and Cobb angle (r = 0.59, P < 0.01), PT (r = 0.49, P = 0.02), TK (r = -0.46, P = 0.03) and TLK (r = 0.44, P = 0.04). Correlations between JOABPQE score and the Cobb angle (r = -0.44, P = 0.04), L3IA (r = -0.53, P = 0.01), PT (r = -0.44, P = 0.04), and TK (r = 0.46, P = 0.03) were also observed. CONCLUSIONS: Cobb angle, L3IA, C7PL-CSVL in coronal plane and PT, TLK in sagittal plane increased, while LL decreased in unilateral DDH patients. These significantly different spinopelvic parameters have no correlation with the extent of dysplasia. Changes in coronal and sagittal plane including Cobb angle, L3IA, PT, TK and TLK were associated with the low back pain in the patients with unilateral DDH.

Negative pressure wound therapy reduces the incidence of postoperative wound dehiscence and surgical site infections after total knee arthroplasty in patients with obesity.

Obesity is a risk factor for total knee arthroplasty (TKA). Wound dehiscence and surgical site infections (SSIs) are the main complications of TKA in patients with obesity. They can profoundly affect patients because they often require readmission, additional surgical interventions, lengthy intravenous antibiotic administration, and delayed rehabilitation. Negative pressure wound therapy (NPWT) exposes the wound site to negative pressure, resulting in the improvement of blood supply, removal of excess fluid, and stimulation of cellular proliferation of granulation tissue. This study aims to assess the incidence of wound dehiscence and SSIs in patients with obesity undergoing TKA after the routine use of NPWT. This sduty enrolled adult patients with obesity who underwent TKA within 8 years. A total of 360 adult patients with obesity (NPWT: 150, non-NPWT: 210) underwent TKA, and the baseline characteristics were similar between the 2 groups. Compared with the non-NPWT group, the NPWT group had a 50% lower incidence of wound dehiscence (3.33% vs 9.52%; P < .05) and a significantly lower incidence of SSIs (11.33% vs 25.24%; P < .05), including prosthetic joint infection (4.0% vs 10.0%; P < .05) and superficial wound infection (7.33% vs 15.24%; P < .05). In addition, the NPWT group had a lower need to return to the operating room for new interventions for any reason (2.67% vs 9.05%; P = .0107) than the non-NPWT group. Conventional incision NPWT can significantly reduce the incidence of wound dehiscence and SSIs in patients with obesity after TKA.

Mechanism of Ferroptosis and Its Role in Spinal Cord Injury.

Ferroptosis is a non-necrotic form of regulated cell death (RCD) that is primarily characterized by iron-dependent membrane lipid peroxidation and is regulated by cysteine transport, glutathione synthesis, and glutathione peroxidase 4 function as well as other proteins including ferroptosis suppressor protein 1. It has been found that ferroptosis played an important role in many diseases, such as neurodegenerative diseases and ischemia-reperfusion injury. Spinal cord injury (SCI), especially traumatic SCI, is an urgent problem worldwide due to its high morbidity and mortality, as well as the destruction of functions of the human body. Various RCDs, including ferroptosis, are found in SCI. Different from necrosis, since RCD is a form of cell death regulated by various molecular mechanisms in cells, the study of the role played by RCD in SCI will contribute to a deeper understanding of the pathophysiological process, as well as the treatment and functional recovery. The present review mainly introduces the main mechanism of ferroptosis and its role in SCI, so as to provide a new idea for further exploration.