Injectable hydrogels activated with copper sulfide nanoparticles for enhancing spatiotemporal sterilization and osteogenesis in periodontal therapy.

Developing biomaterials capable of promoting bone regeneration in bacteria-infected sites is of utmost urgency for periodontal disease therapies. Here we produce a hybrid hydrogel by integrating CuS nanoparticles (CuSNPs), which could kill bacteria through photothermal therapy (PTT) triggered by a near infrared (NIR) light, and a gelatin methacryloyl (GelMA) hydrogel, which is injectable and biocompatible. Specifically, CuSNPs were precipitated by chitosan (CS) firstly, then grafted with methacrylic anhydride (MA) to form CuSNP@CS-MA, which was photo-crosslinked with GelMA to synthesize hybrid hydrogels (GelMA/CuSNP). The hybrid hydrogels exhibited a broad-spectrum antibacterial property that could be spatiotemprorally manipulated through applying a NIR light. Their mechanical properties were adjustable by controlling the concentration of CuSNPs, enabling the hydrogels to become more adapted to the oral diseases. Meanwhile, the hybrid hydrogels showed good cytocompatibility in vitro and improved hemostasis in vivo. Moreover, they accelerated alveolar osteogenesis and vascular genesis, successfully treating periodontis in four weeks in a rat model. GelMA/CuSNP hydrogels showed a broad-spectrum sterilization ability via PTT in vitro and outstanding antibacterial property in vivo, suggesting that the hybrid hydrogels could function in the challenging, bacteria-rich, oral environment. Such injectable hybrid hydrogels, capable of achieving both facilitated osteogenesis and NIR-inducible sterilization, represent a new biomaterial for treating periodontitis.

Skeletal muscle index together with body mass index is associated with secondary osteoporosis in patients with rheumatoid arthritis.

OBJECTIVE: The objective of this study was to explore the associations of body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI) and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA). METHODS: The bone mineral density (BMD) at sites of the femur neck (Neck), total hip (Hip) and lumbar vertebrae 1-4 (L1-4) was measured by dual-energy X-ray absorptiometry. The skeletal muscle index, body fat percentage and mineral content were measured by biological electrical impedance for calculating BMI, FMI and SMI. RESULTS: A total of 433 patient with RA and 158 healthy controls were enrolled. The BMDs at each site of the RA patients were lower compared with those of the healthy controls (p < 0.0001), and the prevalence of OP (36.1%, 160/443) and sarcopenia (65.2%, 288/443) in the RA patients were higher than those in the controls (12.7%, 20/158, p < 0.0001; 9.0%, 14/156, p < 0.0001). Significant differences in the BMD, FMI, SMI, mineral content, body fat percentage and skeletal muscle mass were found among the RA patients in the different BMI groups (p < 0.05). In RA patients with BMI < 18.5 kg/m2, the prevalence of OP in the RA patients with sarcopenia was similar to that in those without sarcopenia (44.4% vs. 66. 7%, χ2 = 0. 574, p = 0.449). In the RA patients with a normal BMI or who were overweight or obese, prevalence of OP in the RA patients with sarcopenia was significantly higher than that in the RA patients without sarcopenia (42.8% vs. 21.7%, χ2 = 10.951, p = 0.001; 61.1% vs. 13.0%, χ2 = 26.270, p < 0.0001). In the RA patients without sarcopenia, the prevalence of OP in the RA patients in the different BMI groups was different (p = 0.039). In the RA patients with sarcopenia, there was no significant difference in the prevalence of OP among the RA patients in the different BMI groups (p = 0. 128). The linear correlation analysis showed that the SMI in RA patients was positively correlated with the BMD of each site measured and BMI and FMI (p < 0.0001). However, there was a negative linear correlation between SMI and disease duration (p = 0.048). The logistic regression analysis found that SMI (OR = 0.569, p = 0.002, 95% CI 0.399-0.810), BMI (OR = 0.884, p = 0.01, 95% CI 0.805-0.971) and gender (1 = female, 2 = male) (OR = 0.097, p < 0.0001, 95% CI 0.040-0.236) were protective factors for OP in RA, while age (OR = 1.098, p < 0.0001, 95% CI 1.071-1.125) was the risk factor. CONCLUSION: BMI and SMI are associated with the occurrence of OP in RA patients, and both SMI and BMI are important protective factors for OP secondary to RA.

Tauroursodeoxycholic acid suppresses biliary epithelial cell apoptosis and endoplasmic reticulum stress by miR-107/NCK1 axis in a FXR-dependent manner.

Tauroursodeoxycholic acid (TUDCA) can activate farnesoid X receptor (FXR) to involve in the formation of gallstones. Here, this study aimed to probe the potential mechanism of TUDCA-FXR network in the formation of bile duct stone. The levels of TUDCA, FXR and NCK1 were decreased, while the level of miR-107 was increased in the serum of bile duct stone patients. FXR expression was positively correlated with TUDCA or NCK1 expression in patients, moreover, TUDCA pretreatment in biliary epithelial cells increased the levels of FXR and NCK1, and rescued the decrease of NCK1 caused by FXR knockdown in cells. Then functional analysis showed FXR knockdown caused apoptosis and endoplasmic reticulum stress (ERS) as well as suppressed proliferation in biliary epithelial cells in vitro, which were attenuated by TUDCA pretreatment or NCK1 overexpression Mechanistically, NCK1 was a target of miR-107, which was up-regulated by FXR silencing, and FXR knockdown-induced decrease of NCK1 was rescued by miR-107 inhibition. Additionally, miR-107 expression was negatively correlated with TUDCA expression in bile duct stone patients, and TUDCA pretreatment in biliary epithelial cells decreased miR-107 expression by FXR. Functionally, the pretreatment of TUDCA or FXR agonist suppressed miR-107-evoked apoptosis and ERS in biliary epithelial cells. In conclusion, TUDCA up-regulates FXR expression to activate NCK1 through absorbing miR-107, thus suppressing the apoptosis and ERS in biliary epithelial cells, these results provided a theoretical basis for elucidating the mechanism of bile duct stone formation.

Association of sarcopenia and vitamin D deficiency with glucocorticoid-induced osteoporosis in Chinese patients with rheumatoid arthritis.

OBJECTIVES: The study aimed to explore the association of sarcopenia and vitamin D deficiency with glucocorticoid-induced osteoporosis (GIOP) in Chinese patients with rheumatoid arthritis (RA). METHOD: Skeletal muscle mass, serum 25(OH)D levels, and bone mineral density (BMD) were assessed. RESULTS: The prevalence of OP, sarcopenia, and vitamin D deficiency in RA patients was significantly higher than in controls (all P < 0.001). The percentage of GC use was 56.9%, and the prevalence of GIOP was 38.1% in 480 RA patients. The prevalence of OP in RA patients without sarcopenia was lower than that in RA patients with sarcopenia (P < 0.05). In RA patients with and without GC, the prevalence of OP in patients without sarcopenia was significantly lower than that in patients with sarcopenia (P < 0.001 and P < 0.05). Female sex (OR = 54.737; 95% CI: 7.103-421.809; P < 0.0001), age (OR = 1.078; 95% CI: 1.048-1.110; P < 0.0001), sarcopenia, and vitamin D deficiency (OR = 2.250; 95% CI: 1.246-64.065; P = 0.007) were risk factors for GIOP in RA patients. CONCLUSIONS: GIOP is associated with sarcopenia and vitamin D deficiency and is widespread among Chinese patients with RA. Key points ·Percentage of using GC and the prevalence of OP were all high in Chinese patients with RA. ·GIOP was widely existed in Chinese RA patients, which was associated with sarcoprnia and vitamin D deficiency.

A dynamic spatiotemporal model for fall warning and protection.

Early detection of falls is important for reducing fall injuries. However, existing fall detection strategies mostly focus on reducing impact injuries rather than avoiding falls. This study proposed the concept of identifying "Imbalance Point" to warn the body imbalance, allowing sufficient time to recover balance. And if falling cannot be avoided, an impact sign is released by detecting the "Fall Point" prior to the impact. To achieve this goal, motion prediction model and balance recovery model are integrated into a spatiotemporal framework to analyze dynamic and kinematic features of body motion. Eight healthy young volunteers participated in three sets of experiment: Normal trial, Recovery trial and Fall trial. The body motion in the trials was recorded using Microsoft Azure Kinect. The results show that the developed algorithm for Fall Point detection achieved 100% sensitivity and 98.6% specificity, along with an average lead time of 297 ms. Moreover, Imbalance Point was successfully detected in all Fall trials, and the average time interval between Imbalance Point and Fall Point was 315 ms, longer than reported step reaction time for elderly (approximately 270 ms). The experiment results demonstrate that the developed algorithm have great potential for fall warning and protection in the elderly.

Association between exposure to mixture of heavy metals and hyperlipidemia risk among U.S. adults: A cross-sectional study.

Previous studies have suggested that exposure to heavy metals might increase the risk of hyperlipidemia. However, limited research has investigated the association between exposure to mixture of heavy metals and hyperlipidemia risk. To explore the independent and combined effects of heavy metal exposure on hyperlipidemia risk, this study involved 3293 participants from the National Health and Nutrition Examination Survey (NHANES), including 2327 with hyperlipidemia and the remaining without. In the individual metal analysis, the logistic regression model confirmed the positive effects of barium (Ba), cadmium (Cd), mercury (Hg), Lead (Pb), and uranium (U) on hyperlipidemia risk, Ba, Cd, Hg and Pb were further validated in restricted cubic splines (RCS) regression model and identified as positive linear relationships. In the metal mixture analysis, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and quantile-based g computation (qgcomp) models consistently revealed a positive correlation between exposure to metal mixture and hyperlipidemia risk, with Ba, Cd, Hg, Pb, and U having significant positive driving roles in the overall effects. These associations were more prominent in young/middle-aged individuals. Moreover, the BKMR model uncovered some interactions between specific heavy metals. In conclusion, this study offers new evidence supporting the link between combined exposure to multiple heavy metals and hyperlipidemia risk, but considering the limitations of this study, further prospective research is required.

Differences of RUNX2 gene promoter methylation and transcription level in ankylosing spondylitis.

BACKGROUND AND OBJECTIVE: Ankylosing spondylitis is a refractory immune disease that seriously affects the life and work of patients. Epigenetic modifications, especially DNA methylation, have become a research hotspot in complex diseases. We aim to explore the changes in runt-related transcription factor 2 (RUNX2) gene promoter methylation and transcription level in AS. METHOD: We detected the RUNX2 gene promoter methylation in 83 AS patients and 83 healthy controls (HCs), then inspected the mRNA difference of RUNX2 between 30 AS patients and 30 HCs by the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The RUNX2 gene promoter was hypomethylated in AS patients compared to HCs (p < .001). The research involved 4 CpG regions and 74 CpG sites of RUNX2, of which CpG-2, CpG-4 regions, and 18 CpG sites have been differentially methylated. The CpG-4 island methylation was negatively correlated with C-reactive protein (p < .05) in AS patients. In the qRT-PCR validation phase, the mRNA level of RUNX2 in AS patients was significantly higher than HCs (p < .05), and in AS patients who were treated with biologics, the methylation level of CpG-2 island showed a negative correlation to mRNA (p < .05). ROC results indicated that RUNX2 methylation and its transcription level have good potential to distinguish AS patients from HCs. CONCLUSION: The RUNX2 gene promoter was hypomethylated in AS patients. Meanwhile, the qRT-PCR verified the up-regulated expression on the transcription level, suggesting the abnormal methylation of RUNX2 contributes to the pathogenesis of AS.

RIOK3 potentially regulates osteogenesis-related pathways in ankylosing spondylitis and the differentiation of bone marrow mesenchymal stem cells.

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.

Causal relationship between endometriosis with infertility and ankylosing spondylitis.

Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = - 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility.

Frailty predicts knee pain trajectory over 9 years: results from the Osteoarthritis Initiative.

OBJECTIVE: Frailty is a multisystem syndrome and its relationship with symptomatic osteoarthritis has been reported. We aimed to identify trajectories of knee pain in a large prospective cohort and to describe the effect of frailty status at baseline on the pain trajectories over 9 years. METHODS: We included 4419 participants (mean age 61.3 years, 58% female) from the Osteoarthritis Initiative cohort. Participants were classified as "no frailty," "pre-frailty," or "frailty" at baseline, based on 5 characteristics (ie, unintentional weight loss, exhaustion, weak energy, slow gait speed, and low physical activity). Knee pain was evaluated annually using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (0-20) from baseline to 9 years. RESULTS: Of the participants included, 38.4%, 55.4%, and 6.3% were classified as "no frailty," "pre-frailty," and "frailty," respectively. Five pain trajectories were identified: "No pain" (n = 1010, 22.8%), "Mild pain" (n = 1656, 37.3%), "Moderate pain" (n = 1149, 26.0%), "Severe pain" (n = 477, 10.9%), and "Very Severe pain" (n = 127, 3.0%). Compared to participants with no frailty, those with pre-frailty and frailty were more likely to have more severe pain trajectories (pre-frailty: odds ratios [ORs] 1.5 to 2.1; frailty: ORs 1.5 to 5.0), after adjusting for potential confounders. Further analyses indicated that the associations between frailty and pain were mainly driven by exhaustion, slow gait speed, and weak energy. CONCLUSIONS: Approximately two-thirds of middle-aged and older adults were frail or pre-frail. The role of frailty in predicting pain trajectories suggests that frailty may be an important treatment target for knee pain.

Polysaccharide-Based Injectable Hydrogels with Fast Gelation and Self-Strengthening Mechanical Kinetics for Oral Tissue Regeneration.

Oral defects lead to a series of function disorders, severely threatening the patients' health. Although injectable hydrogels are widely studied in tissue regeneration, their mechanical performance is usually stationary after implant, without further self-adaption toward the microenvironment. Herein, an injectable hydrogel with programmed mechanical kinetics of instant gelation and gradual self-strengthening along with outstanding biodegradation ability is developed. The fast gelation is realized through rapid Schiff base reaction between biodegradable chitosan and aldehyde-modified sodium hyaluronate, while self-strengthening is achieved via slow reaction between redundant amino groups on chitosan and epoxy-modified hydroxyapatite. The resultant hydrogel also possesses multiple functions including (1) bio-adhesion, (2) self-healing, (3) bactericidal, (4) hemostasis, and (5) X-ray in situ imaging, which can be effectively used for oral jaw repair. We believe that the strategy illustrated here will provide new insights into dynamic mechanical regulation of injectable hydrogels and promote their application in tissue regeneration.

Could endothelial progenitor cells complement the diagnosis of inflammatory arthritis? A systematic review and meta-analysis.

The objective of this meta-analysis was to systematically review existing evidence and evaluate variations in levels of circulating endothelial progenitor cells (EPCs) among individuals with psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA). Relevant studies were identified through database searches, and 20 records were enrolled. We used the fixed-effect model or random-effect model to estimate the pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) in circulating EPC levels between inflammatory arthritis patients and controls. The results showed that circulating EPC levels differed among subtypes of inflammatory arthritis, with significantly lower levels in patients with RA (SMD = -0.848, 95% CI = -1.474 to -0.221, p = 0.008) and PsA (SMD = -0.791, 95% CI = -1.136 to -0.446, p < 0.001). However, no statistically significant difference was found in circulating EPC levels between patients with JIA and controls (SMD = -1.160, 95% CI = -2.578 to 0.259, p = 0.109). Subgroup analyses suggested that in patients with RA, circulating EPC levels were influenced by age, disease activity, and duration. Although many studies have investigated circulating EPC levels in patients with inflammatory arthritis, the results have been inconsistent. This meta-analysis offers a comprehensive overview of the existing evidence and emphasizes the association between levels of circulating EPCs and various types of arthritis. However, further research is needed to determine the specific mechanisms underlying the observed differences in EPC levels in different types of arthritis and to establish the clinical utility of this biomarker.

Clinical features and prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapidly progressive interstitial lung disease in Chinese patients.

OBJECTIVE: The objective of this study is to investigate clinical features and prognostic factors of antimelanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis with rapidly progressive interstitial lung disease (RP-ILD) in Chinese patients. METHODS: Clinical features and prognostic factors of patients with newly diagnosed or recurrent dermatomyositis patients were retrospectively analyzed. All patients were divided into the anti-MDA5-positive or negative dermatomyositis, and with or without RP-ILD groups. Clinical features and prognostic factors were statistically compared among different groups. RESULTS: The serum ferritin (SF) levels (1500.0 [658.80, 1844.0]) and γ-glutamyl transpeptidase (γ-GT) (125.5 [61.0, 232.0] vs. 28 [16.0, 41.0], Z = 5.528; p < .001) were markedly higher, and phosphocreatine myoenzyme (CK) (73.0 [42.0, 201.0] vs. 1333.0 [79.0, 8000.0], Z = -2.739, p = .006), serum albumin level (32.51 ± 5.23 vs. 35.81 ± 5.88, t = -2.542, p = .013), and lymphocyte count (0.80 ± 0.36 vs. 1.45 ± 0.77, t = -4.717, p < .001) were lower than those in anti-MDA5-negative counterparts. Among patients with anti-MDA5 antibody (Ab) with RP-ILD, the SF level (1531.0 [1163.8, 2016.5] vs. 584.9 [564.8, 1042.5], Z = 2.664, p = .008), γ-GT (134.0 [81.0, 204.5] vs. 123.0 [76.0, 189.0], Z = 3.136, p = .002) and positive rate of anti-RO-52 Ab (90.9% vs. 50.0%, χ2 = 7.222, p = .013) were higher and lymphocyte count (0.79 ± 0.38 vs. 1.32 ± 0.74, t = -3.025, p = .029) was lower than those in their counterparts without RP-ILD. The SF level of anti-MDA5 nonsurvivors (1544 [1447.32, 2089.0] vs. 584.9 [515.7, 1500.0], Z = 2.096, p = .030), anti-RO-52 Ab-positive rate ([16/18, 88.9%] vs. [9/16, 56.2%], χ2 = 4.636, p = .031) were higher than those in survivors. Lymphocytopenia was a risk factor for RP-ILD and death of patients with anti-MDA5-positive dermatomyositis. The area under receiver operating characteristic curve was 0.888 (95% confidence interval: 0.756, 1.000; p < .001), the sensitivity was 85.7%, the specificity was 93.8%, and Youden's index was 0.795. CONCLUSIONS: Anti-MDA5-positive dermatomyositis patients are prone to developing RP-ILD. Declined lymphocyte count is a critical risk factor for RP-ILD, probably acting as a simple and effective predictor for Chinese patients with anti-MDA5-positive dermatomyositis.

Global burden and risk factors of musculoskeletal disorders among adolescents and young adults in 204 countries and territories, 1990-2019.

BACKGROUND: Current studies on musculoskeletal (MSK) disorders mainly focus on the elderly, while adolescents and young adults (AYAs) are often neglected despite their unique epidemiology, healthcare needs and societal implications. To bridge this gap, we evaluated the global burden and temporal trends of MSK disorders among AYAs from 1990 to 2019, as well as their common categories and main risk factors. METHODS: Data on the global burden and risk factors of MSK disorders were obtained from the Global Burden of Diseases study 2019. Age standardized rates for incidence, prevalence and disability-adjusted life-years (DALYs) were calculated using the world population age standard, and their temporal trends were evaluated by estimated annual percentage changes (EAPC). Locally estimated scatterplot smoothing (LOESS) regression was used to explore the association between two variables. RESULTS: Over the past 30 years, MSK disorders have become the third leading cause of global DALYs among AYAs, with 36.2%, 39.3%, and 21.2% of increases in incident cases, prevalent cases and DALYs, respectively. In 2019, age standardized incidence, prevalence and DALY rates for MSK disorders were positivity associated with socio-demographic index (SDI) among AYAs in 204 countries and territories. The global age-standardized prevalence and DALY rates of MSK disorders began to increases among AYAs since 2000. In the last decade, countries with high SDI not only presented the only increase in age-standardized incidence rate across all SDI quintiles (EAPC = 0.40, 0.15 to 0.65), but also displayed the most rapid increases in age-standardized prevalence and DALY rates (EAPC = 0.41, 0.24 to 0.57; 0.39, 0.19 to 0.58, respectively). Low back pain (LBP) and neck pain (NP) were the most common MSK disorders among AYAs, accounting for 47.2% and 15.4% of global DALYs of MSK disorders in this population, respectively. Rheumatoid arthritis (RA), osteoarthritis (OA), and gout exhibited increasing trends in global age-standardized incidence, prevalence, and DALY rates among AYAs over the past 30 years (all EAPC >0), whereas LBP and NP showed declining trends (all EAPC <0). Occupational ergonomic factors, smoking and high BMI accounted for 13.9%, 4.3%, and 2.7% of global DALYs for MSK disorders among AYAs, respectively. The proportion of DALYs attributable to occupational ergonomic factors was negatively associated with SDI, whereas the proportions attributable to smoking and high BMI increased with SDI. Over the last 30 years, both the proportions of DALYs attributable to occupational ergonomic factors and smoking have consistently decreased globally and across all SDI quintiles, while the proportion attributable to high BMI has increased. CONCLUSIONS: MSK disorders have emerged as the third leading cause of global DALYs among AYAs over the past three decades. Countries with high SDI should make more efforts to tackle the dual challenges posed by the high levels and rapid increases in age standardized incidence, prevalence, and DALY rates in the last decade.

Association of Sleep Disturbance With Catastrophizing and Knee Pain: Data From the Osteoarthritis Initiative.

OBJECTIVE: To investigate the relationship between sleep disturbance, catastrophizing, and knee pain in middle-aged and older individuals. METHODS: Data from the Osteoarthritis Initiative cohort from months 48 to 96 were used, where month 48 was treated as baseline. Knee pain (Western Ontario and McMaster Universities Osteoarthritis Index pain scale score ≥5 [range 0-20]), catastrophizing (extracted from Coping Strategies Questionnaire score ≥3 [range 0-6]), and sleep quality (extracted from Center for Epidemiologic Studies Depression Scale [range 1-4]) were assessed annually. We described the association of sleep disturbance with the presence and risk of knee pain and catastrophizing. The mediation effect of knee pain and catastrophizing on the sleep-catastrophizing and sleep-pain association was evaluated, respectively. RESULTS: Catastrophizing and knee pain were reported in 346 (10%) and 917 (24%) of the 3,813 participants (mean 64.9 years, 58% female) at baseline. Participants with worse sleep disturbance were more likely to have knee pain (prevalence ratio [PR] 1.4-2.0, P for trend <0.001) and catastrophizing (PR 1.4-3.1, P for trend <0.001). Sleep disturbance at baseline predicted the risk of knee pain (risk ratio [RR] 1.1, P for trend <0.001) and catastrophizing (RR 1.2-1.7, P for trend <0.001) during follow-up. No statistically significant interactions between sleep disturbance and knee pain or catastrophizing were observed. Knee pain and catastrophizing mediated the sleep-catastrophizing and sleep-pain association, respectively, at baseline, and knee pain negatively mediated the sleep-catastrophizing association longitudinally. CONCLUSION: Sleep disturbance was associated with the presence and risk of catastrophizing and knee pain. Sleep interventions may have a universal and independent effect in preventing incident knee pain.

Systemic lupus erythematosus associated with multiple myeloma: Two case reports and a literature review.

INTRODUCTION: Systemic lupus erythematosus (SLE) complicated by multiple myeloma (MM) is a relatively rare clinical presentation, and is easily ignored due to their similar or even identical manifestation, which may lead to misdiagnosis and mistreatment. CASE REPORT: We report two cases of SLE with MM. Case 1 was a 59-year-old male who was diagnosed with SLE 11 years ago. Abnormal kidney function was detected 4 months ago and a bone marrow aspirate revealed MM. He then received three cycles of bortezomib, dexamethasone, and chemotherapy with liposomal doxorubicin, and one cycle of lenalidomide plus dexamethasone. He died of infectious shock. Case 2 was a 58-year-old female who was diagnosed with SLE 27 years ago. After the onset of abnormal renal function 4 years ago, the patient was still treated according to SLE disease activity. When renal function rapidly deteriorated, serum and urine immunofixation electrophoresis was positive for IgG γ with free light chains and she was diagnosed with SLE complicated by MM. She did not agree to the treatment for MM as advised and was discharged from the hospital against medical advice. Case 2 died of cardiac failure. Thirteen cases of SLE with MM reported from 2000 to 2022 in PUBMED and Mendeley and our above two cases were reviewed. Among the 15 patients, 13 were females and 2 were males. The median age at the time of SLE with MM diagnosis was 50 years, and the median time to a delayed diagnosis was 7 years. The serum monoclonal immunoglobulin level was elevated and extramedullary manifestations of renal dysfunction were common. CONCLUSIONS: An elevated monoclonal immunoglobulin level or newly unexplained renal dysfunction occurring in a patient with SLE should prompt monitoring and further screening of MM, rather than treatment as a secondary manifestation of SLE.

Enhanced assessment of human dynamic stability by eliminating the effect of body height: modeling and experiment study.

Margin of stability (MOS) is one of the essential indices for evaluating dynamic stability. However, there are indications that MOS was affected by body height and its application in identifying factors on dynamic stability other than body height is restricted. An inverted pendulum model was used to simulate human walking and investigate the relevance between MOS and body height. Eventually, a height-independent index in dynamic stability assessment (named as Angled Margin of Stability, AMOS) was proposed. For testing, fifteen healthy young volunteers performed walking trials with normal arm swing, holding arms, and anti-normal arm swing. Kinematic parameters were recorded using a gait analysis system with a Microsoft Kinect V2.0 and instrumented walkway. Both simulation and test results show that MOS had a significant correlation with height during walking with normal arm swing, while AMOS had no such significant correlation. Walking with normal arm swing produced significantly larger AMOS than holding arms and anti-normal arm swing. However, no significant difference showed up in MOS between normal arm swing and holding arms. The results suggest that AMOS is not affected by body height and has the potential to identify the variations in dynamic stability caused by physiological factors other than body height.

DNA methylation and transcription of the FOXO3a gene are associated with ankylosing spondylitis.

To explore the association between methylation level and transcript level of Forkhead box O3a (FOXO3a) gene with ankylosing spondylitis (AS) susceptibility. Methylation levels of the FOXO3a promoter were measured in 84 AS patients and 83 healthy controls. A total of 77 patients and 66 healthy subjects were included in subsequent mRNA level testing. DNA methylation levels of 107 CpG sites on 6 CpG islands in the FOXO3a gene were investigated. This study indicated that CpG-4 and CpG-5 islands were markedly hypomethylated in AS patients. The methylation level of CpG-4 island in AS patients was negatively correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Ankylosing Spondylitis Disease Activity Score (ASDAS). Moreover, FOXO3a mRNA levels were significantly decreased in AS patients and were obviously negatively correlated with the methylation levels of CpG-2 and CpG-5 islands in AS patients without treatment. The sensitivity and specificity of differential methylated CpG sites of FOXO3a were 74.7 and 85.4%, respectively. Besides, FOXO3a mRNA had a sensitivity of 80.0% and a specificity of 68.8%. DNA methylation and transcription of FOXO3a might be related to AS susceptibility and play a crucial role in the diagnosis of AS, but many open questions remain.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: A systematic review and meta-analysis of propensity score-matched studies.

Purpose: Laparoscopic liver resection (LLR) is a widely practiced therapeutic method and holds several advantages over open liver resection (OLR) including less postoperative pain, lower morbidity, and faster recovery. However, the effect of LLR for the treatment of hepatocellular carcinoma (HCC) in elderly patients remains controversial. Therefore, we aimed to perform the first meta-analysis of propensity score-matched (PSM) studies to compare the short- and long-term outcomes of LLR versus OLR for elderly patients with HCC. Methods: Databases including PubMed, Embase, Scopus, and Cochrane Library were systematically searched until April 2022 for eligible studies that compared LLR and OLR for the treatment of HCC in elderly patients. Short-term outcomes include postoperative complications, blood loss, surgical time, and length of hospital stay. Long-term outcomes include overall survival (OS) rate and disease-free survival (DFS) rate at 1, 3, and 5 years. Results: A total of 12 trials involving 1,861 patients (907 in the LLR group, 954 in the OLR group) were included. Compared with OLR, LLR was associated with lower postoperative complications (OR 0.49, 95% CI 0.39 to 0.62, P < 0.00001, I 2 = 0%), less blood loss (MD -285.69, 95% CI -481.72 to -89.65, P = 0.004, I 2 = 96%), and shorter hospital stay (MD -7.88, 95% CI -11.38 to -4.37, P < 0.0001, I 2 = 96%), whereas operation time (MD 17.33, 95% CI -6.17 to 40.83, P = 0.15, I 2 = 92%) was insignificantly different. Furthermore, there were no significant differences for the OS and DFS rates at 1, 3, and 5 years. Conclusions: For elderly patients with HCC, LLR offers better short-term outcomes including a lower incidence of postoperative complications and shorter hospital stays, with comparable long-term outcomes when compared with the open approach. Our results support the implementation of LLR for the treatment of HCC in elderly patients. Systematic review registration: https://inplasy.com/inplasy-2022-4-0156/, identifier INPLASY202240156.