BACKGROUND: Body weight has been recognized as a driving factor of osteoarthritis. Few studies had investigated the association between weight status across adulthood and risk of osteoarthritis (OA). This study investigates the association of weight change patterns across adulthood (lasting at least 25 years) with the risk of OA from the National Health and Nutrition Examination Survey (NHANES) 2013-2018.
METHODS: The study assessed the relationship between weight change across adulthood and OA in 7392 individuals aged > 50 spanning a minimum of 25 years. Multivariate linear regression analyses were utilized to detect the association between weight change patterns and self-reported OA. Restricted cubic splines (RCS) were used to examine the nonlinear relationship between absolute weight change and OA risk.
RESULTS: From 10 years ago to survey, the risk of OA was 1.34-fold (95% CI 1.07-1.68) in people changed from obese to non-obese, 1.61-fold (95% CI 1.29-2.00) in people change from non-obese to obese, and 1.82-fold (95% CI 1.49-2.22) in stable obese people compared with people who were at stable normal weight. Similar patterns were also observed at age 25 years to baseline and age 25 years to 10 years before the baseline. The dose-response association of RCS found a U-shaped relationship between absolute weight change and OA risk.
CONCLUSIONS: The study suggests that weight patterns across adulthood are associated with the risk of OA. These findings stressed important to maintain a normal weight throughout adulthood, especially to prevent ignored weight gain in early adulthood to reduce OA risk later.

Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.

This study aimed to determine the function of LINC00511 in NLRP3 inflammasome-mediated chondrocyte pyroptosis via the regulation of miR-9-5p and FUT 1. Chondrocyte inflammatory injury was induced by treating chondrocytes with LPS. Afterwards, the levels of IL-1β and IL-18, the expression of NLRP3, ASC, Caspase-1, and GSDMD, cell viability, and LDH activity in chondrocytes were assessed. LINC00511 expression in LPS-treated chondrocytes was detected, and LINC00511 was subsequently silenced to analyse its role in chondrocyte pyroptosis. The subcellular localization of LINC00511 was predicted and verified. Furthermore, the binding relationships between LINC00511 and miR-9-5p and between miR-9-5p and FUT1 were validated. LINC00511 regulated NLRP3 inflammasome-mediated chondrocyte pyroptosis through the miR-9-5p/FUT1 axis. LPStreated ATDC5 cells exhibited elevated levels of inflammatory injury; increased levels of NLRP3, ASC, Caspase-1, and GSDMD; reduced cell viability; increased LDH activity; and increased LINC00511 expression, while LINC00511 silencing inhibited the NLRP3 inflammasome to restrict LPS-induced chondrocyte pyroptosis. Next, LINC00511 sponged miR-9-5p, which targeted FUT1. Silencing LINC00511 suppressed FUT1 by upregulating miR-9-5p. Additionally, downregulation of miR-9-5p or overexpression of FUT1 neutralized the suppressive effect of LINC00511 knockdown on LPSinduced chondrocyte pyroptosis. Silencing LINC00511 inhibited the NLRP3 inflammasome to quench Caspase-1-dependent chondrocyte pyroptosis in OA by promoting miR-9-5p and downregulating FUT1.

OBJECTIVE: The objective was to investigate the specific role and the regulatory mechanism of vascular endothelial growth factor (VEGF) during wound healing in diabetic foot ulcer (DFU).
METHODS: Streptozotocin-induced diabetic rats were used to establish a DFU animal model. VEGF and Axitinib (a specific inhibitor of VEGFR) were used for treatment in vivo. The wounds at different time points were imaged and histological analysis of the wounds were performed by haematoxylin and eosin (H&E) staining and Masson\'s trichrome staining. Immunohistochemical staining was conducted to examine CD31 and eNOS expression in the wounds. Immunofluorescence assay and quantitative real-time PCR were performed to examine macrophage markers. In addition, THP-1 was differentiated to macrophages, and then treated with interleukin (IL)-4 to induce M2 macrophages, followed by VEGF treatment. The conditional medium (CM) from VEGF-mediated macrophages were collected to culture human dermal fibroblasts (HDFs). Cell viability and migration were measured by Cell Counting Kit (CCK)-8, wound-healing and Transwell assays, respectively.
RESULTS: VEGF treatment remarkably accelerated wound healing of DFU rats. VEGF promoted collagen deposition and elevated CD31 and eNOS expression, confirming the pro-angiogenesis of VEGF around diabetic wound in rats. Meanwhile, VEGF restricted pro-inflammatory cytokines and increased F4/80 and CD206 expression, highlighting the activated macrophages and enhanced M2 macrophages following VEGF treatment in diabetic wounds of DFU rats. However, Axitinib exerted an opposite function to VEGF in DFU rats. Moreover, VEGF directly promoted macrophage polarization toward M2 phenotype in vitro, and the CM from VEGF-mediated M2 macrophages markedly promoted HDFs proliferation, migration and collagen deposition.
CONCLUSIONS: VEGF might accelerate the wound healing of DFU through promoting M2 macrophage polarization and fibroblast migration.

BACKGROUND: Diabetic foot ulcers (DFUs) represent one of the most severe late-stage complications of diabetes. Tibial cortex transverse transport (TTT) surgery stands as the prevailing method for addressing DFUs. This surgical intervention holds the promise of expediting DFU wound healing and diminishing the rate of amputations, with the mitigation of inflammatory responses playing a pivotal role. In this study, we aim to explore the correlation between inflammation and TTT surgery, with the overarching goal of facilitating swift prognostic assessments in clinical practice.
OBJECTIVE: The correlation between the severity of DFUs and clinical test results remains ambiguous. A clinical prediction model was devised to explore the connection between DFU severity and the efficacy of TTT surgery, utilizing straightforward and efficient clinical indicators.
METHODS: Clinical data and examination results were gathered by tracking hospitalized DFU patients who underwent TTT surgery at the First Affiliated Hospital of Guangxi Medical University (Nanning, China). Indicators associated with DFU severity and wound healing time post-surgery were identified through logistic regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Subsequently, a clinical prediction model was constructed. Finally, the intersection of these 2 sets of indicators revealed factors correlated with wound severity and post-operative healing duration.
RESULTS: Our study was comprised of 202 patients who were categorized into 2 groups based on Wagner\'s grading classifications. Utilizing Student\'s t-tests, LASSO regression and logistic regression analyses, we identified 3 factors indicative of DFU severity: platelet-to-lymphocyte ratio (PLR), mixed lymphocyte reaction (MLR) and hemoglobin (HGB). Univariate COX regression analysis revealed 12 factors such as: white blood cells (WBC), neutrophils (NEUT), monocytes (MO), PLR, MLR, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), age, lymphocytes (LY), monocyte-to-neutrophil ratio (MNR), uric acid (UA), and albumin (ALB) associated with the postoperative healing duration. Ultimately, we identified 2 factors, PLR and MNR, at the intersection of these 2 datasets.
CONCLUSIONS: Platelet-to-lymphocyte ratio and MNR were identified as factors associated with both the severity of DFUs and the prognosis following TTT surgery.

BACKGROUND: Abnormal immune responses, particularly T-cell activity, are linked to vascular complications in hypertension, but mechanisms remain unknown. Our study aims to explore the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and T-cell receptor (TCR) repertoires in essential hypertension patients, focusing on understanding the role of T cells in the development of arterial stiffness in this population.
METHODS: The study included 301 essential hypertension patients and 48 age-matched normotensive controls. Essential hypertension patients were stratified into high (baPWV ≥1400 cm/s, n = 213) and low (baPWV <1400 cm/s, n = 88) baPWV groups. High-throughput sequencing analyzed peripheral TCRβ repertoires.
RESULTS: Significant TCRβ repertoire differences were observed between essential hypertension and normotensive groups, as well as between high and low baPWV essential hypertension subgroups. Specifically, patients in the high baPWV group exhibited notable variations in the utilization of specific TCR beta joining (TRBJ) and variable (TRBV) genes compared to the low baPWV group. These alterations were accompanied by reduced TCRβ diversity (represented by diversity 50 s), increased percentages of the largest TCRβ clones, and a higher number of TCRβ clones exceeding 0.1%. The presence of specific TCRβ clones was detected in both groups. Furthermore, reduced diversity 50s and elevated percentages of the largest TCRβ clones were independently correlated with baPWV, emerging as potential risk factors for increased baPWV in essential hypertension patients.
CONCLUSIONS: TCR repertoires were independently associated with arterial stiffness in patients with essential hypertension, implicating a potential role for dysregulated T-cell responses in the pathogenesis of arterial stiffness in this patient population.Trial registration: ChiCTR2100054414.

UNASSIGNED: The incidence of Crohn\'s disease (CD) and rheumatoid arthritis (RA) co-morbidity, as well as the number of individuals affected, is on the rise due to their shared molecular and cellular factors. This study aimed to identify potential therapeutic targets and medicines for comorbid CD and RA.
UNASSIGNED: We integrated single-cell RNA sequencing, Mendelian randomization, and colocalization analysis results from public databases to analyse immune cell subgroups in CD and RA patients and identify candidate therapeutic targets. We further screened potential medicines for the identified candidate targets using the Comparative Toxicogenomics Database (CTD) and molecular docking and molecular dynamics simulations.
UNASSIGNED: The proportion of CD8 effector memory T cells (Tem) was consistently elevated in the peripheral blood mononuclear cells (PBMCs) of both CD and RA patients. MYBL1 had a causal effect on the onset of both CD (OR = 1.23; 95 % CI, 1.05-1.45; P = 0.046) and RA (OR = 1.45; 95 % CI, 1.14-1.85; P = 0.04). Four potential therapeutic molecules were retrieved from the CTD database, among which tretinoin (docking score: -6.3 kcal/mol) showed the best potential.
UNASSIGNED: Our comprehensive analysis suggests that CD8 Tem cells are a key cell group in comorbid RA and CD and that MYBL1 has a causal effect. Tretinoin was identified as a potential targeted therapeutic drug, which is of great clinical research value.

UNASSIGNED: Despite the fact that China amounts to one-fifth of the world\'s population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men.
UNASSIGNED: Building upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant.
UNASSIGNED: A diet rich in \"carnivorous\", \"vegetarian\", \"dairy, fruit, and egg\" was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1-4 (L1-4). Yet, a diet rich in \"beverage and fried food\" was associated with a lower BMD at the FN and L1-4. High quartiles of the carnivorous diet were associated with 34%-39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures.
UNASSIGNED: Our study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1-4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

UNASSIGNED: The study aimed to investigate the diagnostic values of different musculoskeletal ultrasound (MSUS) signs, serum uric acid (SUA), and their combined detection for gouty arthritis (GA).
UNASSIGNED: In this retrospective study, 70 patients (62 males, 8 females; mean age: 46.1±14.1 years; range, 25 to 86 years) diagnosed with GA (the GA group) between August 2022 and March 2023 and 70 patients (54 females, 16 males; mean age: 49.0±14.1 years; range, 21 to 75 years) diagnosed with rheumatoid arthritis and osteoarthritis during the same period (the non-GA group) were included. The positive rate of MSUS signs and SUA in both groups was recorded to compare the differences. The correlations of MSUS signs and SUA with GA were analyzed using Spearman\'s rank correlation analysis. The diagnostic values of different MSUS signs, SUA, and their combined detection for GA were analyzed using a receiver operating characteristic, the area under the curve (AUC), sensitivity, specificity, and the Youden index.
UNASSIGNED: The positive rate of the double contour (DC) sign (chi-squared [χ2 ]=102.935, p<0.001), hyperechoic spots (χ2=56.395, p<0.001), bone erosions (χ2 =10.080, p<0.001), and SUA (χ2 =41.117, p <0.001) were higher in the GA group than in the non-GA group. The positive rate of the DC sign (rs=0.829, p=0.001), hyperechoic spots (rs=0.631, p<0.001), bone erosion (rs=0.268, p=0.001), and SUA (rs=0.542, p<0.001) were positively correlated with GA. Among the single-indicator measures, the DC sign exhibited the highest diagnostic value (AUC=0.907, sensitivity=81.4%, specificity=100%, p<0.001). Among the combined-indicator measures, the DC sign combined with SUA exhibited the highest diagnostic value (AUC=0.929, sensitivity=91.4%, specificity=94.3%, p<0.001), higher than DC sign detection alone.
UNASSIGNED: The DC sign combined with SUA yielded a high diagnostic value and can thus provide a reliable basis for effectively and efficiently diagnosing GA.

This study aimed to develop and validate a bone marrow edema model using a magnetic resonance imaging-based radiomics nomogram for the diagnosis of osteoarthritis. Clinical and magnetic resonance imaging (MRI) data of 302 patients with and without osteoarthritis were retrospectively collected from April 2022 to October 2023 at Longhua Hospital affiliated with the Shanghai University of Traditional Chinese Medicine. The participants were randomly divided into two groups (a training group, n = 211 and a testing group, n = 91). We used logistic regression to analyze clinical characteristics and established a clinical model. Radiomics signatures were developed by extracting radiomic features from the bone marrow edema area using MRI. A nomogram was developed based on the rad-score and clinical characteristics. The diagnostic performance of the three models was compared using the receiver operating characteristic curve and Delong\'s test. The accuracy and clinical application value of the nomogram were evaluated using calibration curve and decision curve analysis. Clinical characteristics such as age, radiographic grading, Western Ontario and McMaster Universities Arthritis Index score, and radiological features were significantly correlated with the diagnosis of osteoarthritis. The Rad score was constructed from 11 radiological features. A clinical model was developed to diagnose osteoarthritis (training group: area under the curve [AUC], 0.819; testing group: AUC, 0.815). Radiomics models were used to effectively diagnose osteoarthritis (training group,: AUC, 0.901; testing group: AUC, 0.841). The nomogram model composed of Rad score and clinical characteristics had better diagnostic performance than a simple clinical model (training group: AUC, 0.906; testing group: AUC, 0.845; p < 0.01). Based on DCA, the nomogram model can provide better diagnostic performance in most cases. In conclusion, the MRI-bone marrow edema-based radiomics-clinical nomogram model showed good performance in diagnosing early osteoarthritis.