Global burden of early-onset osteoarthritis, 1990-2019: results from the Global Burden of Disease Study 2019.

OBJECTIVES: Early-onset osteoarthritis (OA) is an emerging health issue amidst the escalating prevalence of overweight and obesity. However, there are scant data on its disease, economic burden and attributable burden due to high body mass index (BMI). METHODS: Using data from the Global Burden of Diseases Study 2019, we examined the numbers of incident cases, prevalent cases, years lived with disability (YLDs) and corresponding age-standardised rates for early-onset OA (diagnosis before age 55) from 1990 to 2019. The case definition was symptomatic and radiographically confirmed OA in any joint. The average annual percentage changes (AAPCs) of the age-standardised rates were calculated to quantify changes. We estimated the economic burden of early-onset OA and attributable burden to high BMI. RESULTS: From 1990 to 2019, the global incident cases, prevalent cases and YLDs of early-onset OA were doubled. 52.31% of incident OA cases in 2019 were under 55 years. The age-standardised rates of incidence, prevalence and YLDs increased globally and for countries in all Sociodemographic Index (SDI) quintiles (all AAPCs>0, p<0.05), with the fastest increases in low-middle SDI countries. 98.04% of countries exhibited increasing trends in all age-standardised rates. Early-onset OA accounts for US$46.17 billion in healthcare expenditure and US$60.70 billion in productivity loss cost in 2019. The attributable proportion of high BMI for early-onset OA increased globally from 9.41% (1990) to 15.29% (2019). CONCLUSIONS: Early-onset OA is a developing global health problem, causing substantial economic costs in most countries. Targeted implementation of cost-effective policies and preventive intervention is required to address the growing health challenge.

Phenotypes of osteoarthritis-related knee pain and their transition over time: data from the osteoarthritis initiative.

BACKGROUND: Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes. METHODS: Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes. RESULTS: In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among "Mild P-A" at baseline, 32.0% converted to no-pain, 12.8% progressed to "Mild P-R-A", and 53.2% remained. Approximately 46.1% of "Mild P-R-A" and 54.5% of "Mod P-R-A" at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade. CONCLUSIONS: We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes.

Dysbiosis of gut microbiota, a potential mediator of bile acid compositions, and prevalence of hand synovitis: a community-based study.

OBJECTIVES: Hand synovitis, a potentially modifiable pathological lesion, is common and associated with pain and hand OA; nevertheless, its pathogenesis remains uncertain. This study investigated the relationship between gut microbiota dysbiosis and hand synovitis prevalence and evaluated whether bile acids mediate the association. METHODS: Participants were derived from a community-based observational study. Synovitis in each hand joint was assessed using US. Gut microbiota was evaluated using 16S ribosomal RNA amplicon sequencing on faeces, and plasma bile acids were measured by HPLC mass spectrometry. We examined the relationship between gut microbiota dysbiosis and hand synovitis prevalence, as well as the extent to which bile acids were involved in the association. RESULTS: Among 1336 participants (mean age: 63.2 years; women: 58.8%), 18.3% had prevalent hand synovitis (unilateral in 13.6% and bilateral in 4.7%). ß-diversity, but not α-diversity, of gut microbiota was significantly associated with prevalent hand synovitis. Higher relative abundance of the genus Prevotella and lower relative abundance of the genus Blautia were significantly associated with the prevalence of hand synovitis. Similar associations were also observed for laterality and the number of joints affected by hand synovitis. The association between Prevotella and hand synovitis was partially mediated through its effect on tauroursodeoxycholic acid and glycoursodeoxycholic acid, the mediation proportions being 25.7% and 21.6%, respectively. CONCLUSION: Our findings suggest that gut microbiota dysbiosis is associated with the prevalence of hand synovitis. Such an association appears to be partially mediated by plasma bile acids.

Twistocaloric Modeling of Elastomer Fibers and Experimental Validation.

The twistocaloric effect is attributed to the change in entropy of the material driven by torsional stress. It is responsible for the torsional refrigeration of fiber materials that has been widely exploited as one of the solid-state cooling techniques with high efficiency and low volume change rate. The lack of theories and mathematical models of twistocaloric effect, however, limits broad applications of torsional refrigeration. In this work, a twistocaloric model is established to capture the relationship between twist density and temperature variation of natural rubber fibers and thermoplastic elastomer yarns. An experimental setup consisting torsion actuator and torque sensor coupled with a temperature measurement system is built to validate the model. Using the Maxwell relationship, twistocaloric coefficient is measured by quantifying the thermal effect induced by torsion under shear strain. The experimental characterization of the twistocaloric effect in natural rubber fiber and thermoplastic elastomer yarn are consistent with the theoretical predictions.

Prevalence and distribution of ultrasound-detected hand synovial abnormalities in a middle-aged and older population.

OBJECTIVE: Synovial abnormalities are modifiable targets for hand pain and osteoarthritis. We examined the prevalence and distribution of ultrasound-detected hand synovial abnormalities in a community-derived sample of older people in China. METHODS: Within the Xiangya Osteoarthritis Study, a community-based study, we assessed synovial hypertrophy (SH), joint effusion, and Power Doppler signal (PDS) on all fingers and thumbs of both hands using standardized ultrasound examinations (score: 0-3). We assessed distribution patterns of SH and effusion using χ2-test and interrelationships of SH and effusion in different joints and hands by generalized estimating equations. RESULTS: Among 3,623 participants (mean age: 64.4 years; women: 58.1%), prevalence of SH, effusion and PDS were 85.5%, 87.3% and 1.5%, respectively. Prevalence of SH, effusion and PDS increased with age, was higher in the right hand than in the left hand and was more common in proximal than in distal hand joints. SH and effusion often occurred in multiple joints (P < 0.001). SH in one joint was strongly associated with presence of SH in the same joint of the opposite hand (odds ratio [OR]= 6.60, 95% confidence interval [CI]: 6.19-7.03) followed by SH in other joints in the same row, (OR=5.70, 95%CI: 5.32-6.11), and then other joints in the same ray of the same hand (OR=1.49, 95%CI: 1.39-1.60). Similar patterns were observed for effusion. CONCLUSION: Hand synovial abnormalities are common among older people, often affect multiple hand joints and present a unique pattern. These findings suggest both systemic and mechanical factors play roles in their occurrence.

TOR kinase, a GPS in the complex nutrient and hormonal signaling networks to guide plant growth and development.

To survive and sustain growth, sessile plants have developed sophisticated internal signalling networks that respond to various external and internal cues. Despite the central roles of nutrient and hormone signaling in plant growth and development, how hormone-driven processes coordinate with metabolic status remains largely enigmatic. Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrients, growth factors, hormones, and stress signals to promote growth in all eukaryotes. Inspired by recent comprehensive systems, chemical, genetic, and genomic studies on TOR in plants, this review discusses a potential role of TOR as a 'global positioning system' that directs plant growth and developmental programs both temporally and spatially by integrating dynamic information in the complex nutrient and hormonal signaling networks. We further evaluate and depict the possible functional and mechanistic models for how a single protein kinase, TOR, is able to recognize, integrate, and even distinguish a plethora of positive and negative input signals to execute appropriate and distinct downstream biological processes via multiple partners and effectors.

Associations between adipokines gene polymorphisms and knee osteoarthritis: a meta-analysis.

BACKGROUND: Adipokines gene polymorphisms are speculated to be associated with the risk of knee osteoarthritis (OA), but evidence remains conflicting. This study therefore aimed to examine whether associations exist between adipokines gene polymorphisms and knee OA by considering the evidence collected from eligible studies through a meta-analysis. METHODS: A systematic search was performed on PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang up to March 31, 2020. Meta-analysis was carried out by focusing on the associations between adipokines gene polymorphisms and knee OA with the allele model, dominant model, and recessive model. RESULTS: The present meta-analysis included 5 eligible studies for ADIPOQ rs1501299 with 1,021 cases and 1,097 controls, 3 eligible studies for ADIPOQ rs2241766 with 549 cases and 544 controls, 3 eligible studies for LEPR rs1137101 with 808 cases and 856 controls, 2 eligible studies for VISFATIN rs4730153 with 339 cases and 680 controls and 2 eligible studies for VISFATIN rs16872158 with 339 cases and 680 controls. Significant association was observed between LEPR rs1137101 and knee OA in the overall population (recessive: OR = 0.40, 95% CI 0.21-0.79). Limited data revealed that associations may exist between ADIPOQ rs2241766 and knee OA in Asians (dominant: OR = 1.35, 95% CI 1.03-1.78), between VISFATIN rs4730153 and knee OA in Asians (allele: OR = 0.58, 95% CI 0.41-0.83; dominant: OR = 0.57, 95% CI 0.39-0.83), and between VISFATIN rs16872158 and knee OA in Asians (allele: OR = 1.84, 95% CI 1.26-2.68; dominant: OR = 1.94, 95% CI 1.31-2.89). CONCLUSIONS: Adipokines gene polymorphisms may be associated with knee OA. The association was observed in LEPR rs1137101 in the present study. In addition, limited data revealed that associations may also exist in ADIPOQ rs2241766, VISFATIN rs4730153 and VISFATIN rs16872158. PROSPERO REGISTRATION: CRD42020187664.

Risks of Ischemic Stroke/Transient Ischemic Attack Based on CHA2DS2-VASc Scores in Non-Atrial Fibrillation Chinese Patients with Sinus Rhythm.

This study aims to evaluate the incidence of ischemic stroke or transient ischemic attack (TIA) based on CHA2DS2-VASc scores in non-AF Chinese patients with sinus rhythm.We used health check-up data of 101,510 participants from the Kailuan Cohort Study. Participants' risk levels were defined by their CHA2DS2-VASc scores (range 0-3): Men with scores of 0, 1, or ≥ 2 and women with scores of 1, 2, or ≥ 3 were considered at low, intermediate, or high risk, respectively. Cox proportional hazards model was used to assess the association between the CHA2DS2-VASc-determined risk and the incidence of ischemic stroke/TIA.The mean 7.5 year follow-up examination revealed 2968 ischemic strokes/TIA events. The incidence rates for ischemic stroke/TIA events in men and women were 3.8% and 1.5%, respectively. The incidence of ischemic stroke/TIA increased with elevated predicted risks based on CHA2DS2-VASc scores in men: 2.2% for low-risk, 4.1% for intermediate-risk, and 7.8% for high-risk groups (P < 0.001 for trend). The incidences of ischemic stroke/TIA also increased with elevated predicted risks in women: 0.8% for low-risk, 2.1% for intermediate-risk, and 5.0% for high-risk groups (P < 0.001 for trend). Compared with low-risk group, the crude hazard ratio (95% confidence interval) of ischemic stroke/TIA for men in moderate- and high-risk groups were 1.96 (1.79-2.14; P < 0.001) and 4.18 (3.81-4.57; P < 0.001). Similar findings were observed in women.Risks of ischemic stroke/TIA events was high, particularly among those with high CHA2DS2-VASc scores.

Association between dietary selenium intake and the prevalence of osteoporosis: a cross-sectional study.

OBJECTIVE: To examine the correlation between dietary selenium (Se) intake and the prevalence of osteoporosis (OP) in the general middle-aged and older population in China. METHODS: Data for analyses were collected from a population based cross-sectional study performed at the Xiangya Hospital Health Management Centre. Dietary Se intake was evaluated using a validated semi-quantitative food frequency questionnaire. OP was diagnosed on the basis of bone mineral density scans using a compact radiographic absorptiometry system. The correlation between dietary Se intake and the prevalence of OP was primarily examined by multivariable logistic regression. RESULTS: This cross-sectional study included a total of 6267 subjects (mean age: 52.2 ± 7.4 years; 42% women), and the prevalence of OP among the included subjects was 9.6% (2.3% in men and 19.7% in women). Compared with the lowest quartile, the energy intake, age, gender and body mass index (BMI)-adjusted odds ratios of OP were 0.72 (95% confidence interval [CI] 0.55-0.94), 0.72 (95% CI 0.51-1.01) and 0.47 (95% CI 0.31-0.73) for the second, third and fourth quartiles of dietary Se intake, respectively (P for trend = 0.001). The results remained consistent in male and female subjects. Adjustment for additional potential confounders (i.e., smoking status, drinking status, physical activity level, nutritional supplements, diabetes, hypertension, fibre intake, and calcium intake) did not cause substantial changes to the results. CONCLUSIONS: In the middle-aged and older humans, participants with lower levels of dietary Se intake have a higher prevalence of OP in a dose-response manner.

Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies.

OBJECTIVES: To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA). METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies. RESULTS: 43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=-0.30, 95% CI -0.40 to -0.20) and improving function (SMD=-0.35, 95% CI -0.45 to -0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=-0.81, 95% CI -1.12 to -0.52) and piroxicam was most effective for functional improvement (SMD=-1.04, 95% CI -1.60 to -0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs. CONCLUSIONS: Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study.

[Association between red blood cell volume distribution width and osteophytes: A cross-sectional study].

OBJECTIVE: To investigate the association between red blood cell volume distribution width (RDW) and osteophytes.
 Methods: This cross-sectional study was conducted in the Department of Health Examination Center of Xiangya Hospital, Central South University in Changsha, Hunan Province, China. A total of 8 334 subjects were included in this study. The severity of osteophytes was graded using the criteria of the Osteoarthritis Research Society International (OARSI). Osteophytes incident was defined as at least one side of the knee had a osteophytes grade ≥1. According to the quartiles of the RDW level, the subjects were divided into 4 groups. Multivariate logistic regression analysis was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) of the knee osteophytes incidence between each RDW group and the lowest level group. Tests for linear trends were conducted based on logistic regression using a median variable of RDW level in each category.
 Results: Quartile 1 (Q1), RDW≤9.78; Q2, 9.7813.10. The multivariable adjusted ORs (95%CI) of the prevalence of osteophytes were 1.38 (1.06 to 1.79) in the second percentile interval, and 1.27 (0.97 to 1.66) and 1.50 (1.15 to 1.94) in the third and fourth percentile interval, respectively. Test for linear trends suggested that there was a positive association between the RDW level and the risk of knee osteophytes incidence (P=0.019).
 Conclusion: The risk of osteophytes incidence increases with the increasing RDW levels.

Base-Promoted (5 + 2) Annulation between 2-(Alkynylaryl)acetonitriles and Arylalkynes for the Synthesis of Benzocycloheptene Derivatives.

Herein, we describe a novel approach to the synthesis of benzocycloheptene derivatives via base-promoted (5 + 2) annulation between 2-(alkynylaryl)acetonitriles and arylalkynes. In this chemistry, 2-(alkynylaryl)acetonitriles are employed as a new C5 synthon to construct various benzocycloheptene(s) derivatives by building two C-C bonds in one single step. This method features excellent regioselectivity, the use of readily available starting materials, and good functional group tolerance. The practicality of the strategy was further demonstrated by gram-scale synthesis, late-stage functionalizations, and the post-modification of natural products such as probenecid and tetrahydrofurfuryl alcohol.

The Diagnostic Accuracy and Cutoff Value of Phase Angle for Screening Sarcopenia: A Systematic Review and Meta-Analysis.

OBJECTIVES: Phase angle (PhA) declines with age and is a reliable marker for muscle function, making it a potential screening indicator for sarcopenia. However, studies examined the reliability and validity of PhA for detecting sarcopenia, yielding inconsistent results. This meta-analysis aimed to evaluate the accuracy and cutoff value of PhA for screening sarcopenia and examine the potential confounding factors. DESIGN: This is a meta-analysis. SETTING AND PARTICIPANTS: PubMed, Embase, and Cochrane Library were searched up to September 18, 2023.Eighteen studies (6184 participants) were included reporting the diagnostic accuracy of PhA for screening sarcopenia. METHODS: Pooled accuracy (ie, the computed area under the curve value [AUC]) and cutoff value interval for screening sarcopenia were estimated using a random-effects model. Meta-regression analyses were conducted to identify sources of heterogeneity. RESULTS: The AUC value was 0.81. Pooled sensitivity and specificity were 80% and 70%. The calculated 95% CI of the cutoff value of PhA for screening sarcopenia falls between 4.54° and 5.25°. The results of meta-regression analyses showed that ethnicity, body mass index (BMI), health status, and diagnostic criteria were the main factors affecting the diagnostic accuracy for screening sarcopenia (with all P values < 0.01). CONCLUSION AND IMPLICATIONS: PhA may serve as a robust screening tool for sarcopenia, and the recommended cutoff interval falls between 4.54° and 5.25°. Ethnicity, BMI, health status, and diagnostic criteria can affect PhA's efficacy in sarcopenia screening.

Efficient solar-driven crude oil cleanup via graphene/cellulose aerogel with radial and centrosymmetric design.

Frequent oil spills pose significant threats to ecosystems; therefore, strict requirements are needed for prompt remediation and reclamation of spilled oil. Influenced by the structure of coniferous trees and their water transport, this experiment used cellulose nanofiber (CNF), polyvinyl alcohol (PVA), and methyltrimethoxysilane (MTMS) to prepare radially centrosymmetric aerogels. By utilizing the in-situ polycondensation reaction of MTMS, CNF, and PVA were connected, and the hydrophobicity and mechanical properties of the aerogel were greatly enhanced. Furthermore, the introduction of graphene oxide (GO), enshrouded within the cross-linked network, engenders heightened photo-thermal effects. The resultant composite aerogel exhibits expeditious oil absorption under solar irradiation and radial layered channel architecture, significantly curtailing the crude oil absorption timeframe (achieving a maximum absorption capacity of 51.7 g/g). Moreover, it demonstrates superior performance in rapidly and repeatedly adsorbing highly viscous crude oil, surpassing existing literature. Notably, continuous absorption of high-viscosity crude oil is achieved by integrating the composite aerogel with a peristaltic pump. This study offers a novel approach to the absorption and retrieval of high-viscosity crude oil, broadening the potential application horizons of CNF-based aerogels within environmental remediation.

Dapagliflozin: A sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced atrial fibrillation by regulating atrial electrical and structural remodeling.

AIM: Atrial fibrillation (AF), the most common arrhythmia, is characterized by atrial electrical and structural remodeling. Previous studies have found that sodium-glucose cotransporter 2 inhibitor (SGLT2i) can protect myocardium in a glucose independent mechanism. But the role of SGLT2i in regulating AF remains largely unknown. This study, we aimed to investigate the effect of Dapagliflozin (DAPA) in reducing AF susceptibility via inhibiting electrical and structural remodeling. METHOD: The mouse model was established by Angiotensin II (2000 ng/kg/min) infusion for 3 weeks, and an in vitro model was generated by stimulating HL-1 and primary mouse fibroblast with Ang II (1 µM) for 24 h. Programmed electrical stimulation, ECG and whole-cell patch clamp were used to detect DAPA effect on atrial electrical remodeling induced by Ang II. To observe DAPA effect on atrial structural remodeling induced by Ang II, we used echocardiographic, H&E and Masson staining to evaluate atrial dilation. To further explore the protective mechanism of DAPA, we adopt in silico molecular docking approaches to investigate the binding affinity of Ang II and CaMKII at Met-281 site. Western blot was to detect expression level of CaMKII, ox-CaMKII, Nav1.5, Kv4.3, Kv4.2, Kchip2, Kir2.1 and Cx40. RESULTS: Ang II induced AF, atrial dilatation and fibrosis, led to atrial electrical and structural remodeling. However, these effects were markedly abrogated by DAPA treatment, a specific SGLT2i. Our observation of atrial electrical activity in mice revealed that DAPA could rescue the prolonged action potential duration (APD) and the abnormal currents of IK1, Ito and INaL triggered by Ang II infusion. DAPA could reduce the binding affinity of Ang II and CaMKII at Met-281 site, which indicated that DAPA may directly alleviate the activation of CaMKII caused by Ang II. DAPA could reduce the upregulation of ox-CaMKII caused by Ang II infusion in atrial tissues. Moreover, DAPA also ameliorated the aberrant expression levels of electrical activity related proteins (Nav1.5, Kv4.3, Kv4.2, Kchip2, Kir2.1 and Cx40) and fibrosis related signal pathways (TGF-ß1, p-smad/smad) caused by Ang II. Furthermore, we confirmed that DAPA, as well as other SGLT2i (EMPA, CANA), could reverse these abnormalities caused by Ang II incubation in HL-1 cells and primary mouse fibroblasts, respectively. CONCLUSION: Overall, our study identifies DAPA, a widely used SGLT2i, contributes to inhibiting Ang II-induced ox-CaMKII upregulation and electrical and structural remodeling to reduce AF susceptibility, suggesting that DAPA may be a potential therapy of treating AF.

Bidirectional association identified between synovitis and knee and hand osteoarthritis: a general population-based study.

Background: Synovitis has long been considered a common and modifiable inflammatory feature of osteoarthritis (OA), but current disease-modifying anti-inflammatory treatments appear ineffective in OA clinical trials. Elucidating the temporal relationship between synovitis and OA could provide insight into the role of synovitis in OA. Methods: We conducted a prospective cohort study based on the baseline and three-year follow-up data from the Xiangya Osteoarthritis (XO) Study. We assessed bidirectional associations between ultrasound-detected synovitis and radiographic and symptomatic OA at knee and hand sites using generalized estimating equations. Additionally, we performed bidirectional Mendelian randomization (MR) analyses to test these hypotheses utilising whole-genome sequencing data in the XO population. Age, sex, body mass index, smoking, alcohol consumption, educational level, physical activity, and joint injury history were adjusted for these analyses. Findings: A total of 2211, 2420, 2280, and 2600 participants were enrolled for analyses of radiographic knee OA (RKOA), symptomatic knee OA (SKOA), radiographic hand OA (RHOA) and symptomatic hand OA (SHOA), respectively. The baseline synovitis (i.e., with synovitis vs. without synovitis) was associated with the incident RKOA (76/277 vs. 557/3674 knees), SKOA (49/387 vs. 287/4213 knees), RHOA (171/358 vs. 686/3664 hands) and SHOA (35/689 vs. 76/4327 hands), with adjusted odds ratio (aORs) of 2.2 (95% CI 1.7-3.1), 2.0 (1.3-2.9), 3.4 (2.7-4.4), and 2.4 (1.5-3.8), respectively. The baseline RKOA (with OA vs. without OA: 409/1246 vs. 481/3758 knees), SKOA (200/576 vs. 675/4356 knees), RHOA (192/778 vs. 410/3723 hands), and SHOA (41/162 vs. 548/4285 hands) were also associated with the incident synovitis, with aORs of 3.4 (95% CI 2.9-4.1), 2.7 (2.1-3.4), 2.3 (1.8-2.9) and 1.9 (1.2-2.8), respectively. These bidirectional associations were stronger when more active synovitis was compared with the reference group (all P < 0.05). MR analyses further supported bidirectional associations that synovitis significantly increased the odds of incident OA at both sites and vice versa (all ORs ranged from 1.2-1.7). Interpretation: Our population-based cohort study found novel evidence of a bidirectional association between synovitis and OA, which was further validated through MR analysis and suggested that the bidirectional association is likely causal. Our findings indicated that synovitis is both a risk factor and a consequence of the OA rather than solely a risk factor. Funding: The National Key Research and Development Plan, the National Natural Science Foundation of China, the Key Research and Development Program of Hunan Province, the Natural Science Foundation of Hunan Province, the Central South University Innovation-Driven Research Programme, and the Fundamental Research Funds for the Central Universities of Central South University.

Association Between Hyperuricemia and Ultrasound-Detected Hand Synovitis.

OBJECTIVE: Although hand synovitis is prevalent in the older population, the etiology remains unclear. Hyperuricemia, a modifiable metabolic disorder, may serve as an underlying mechanism of hand synovitis, but little is known about their relationship. We assessed the association between hyperuricemia and hand synovitis in a large population-based sample. METHODS: We performed a cross-sectional study in Longshan County, Hunan Province, China. Hyperuricemia was defined as a serum urate level >420 µmol/L in men and >360 µmol/L in women. Ultrasound examinations were performed on both hands of 4,080 participants, and both gray-scale synovitis and the Power Doppler signal (PDS) were assessed using semiquantitative scores (grades 0-3). We evaluated the association of hyperuricemia with hand gray-scale synovitis (grade ≥2) and PDS (grade ≥1), respectively, adjusting for age, sex, and body mass index. RESULTS: All required assessments for analysis were available for 3,286 participants. The prevalence of hand gray-scale synovitis was higher among participants with hyperuricemia (30.0%) than those with normouricemia (23.3%), with an adjusted odds ratio (aOR) of 1.28 (95% confidence interval [CI] 1.00-1.62). Participants with hyperuricemia also had a higher prevalence of PDS (aOR 2.36; 95% CI 1.15-4.81). Furthermore, hyperuricemia positively associated, both at the hand and joint levels, with the presence of gray-scale synovitis (aOR 1.27; 95% CI 1.00-1.60 and adjusted prevalence ratio [aPR] 1.26; 95% CI 1.10-1.44, respectively) and PDS (aOR 2.35; 95% CI 1.15-4.79 and aPR 2.34; 95% CI 1.28-4.30, respectively). CONCLUSION: This population-based study provides more evidence for a positive association between hyperuricemia and prevalent hand synovitis.

Hyperhomocysteinaemia Promotes Doxorubicin-Induced Cardiotoxicity in Mice.

Doxorubicin, a widely used chemotherapeutic drug in clinical oncology, causes a series of cardiac side effects referred to as doxorubicin-induced cardiotoxicity. Hyperhomocysteinaemia is an independent risk factor for multiple cardiovascular diseases. However, whether hyperhomocysteinaemia contributes to doxorubicin-induced cardiotoxicity is currently unknown. In this study, we explored the pathogenic effects of hyperhomocysteinaemia induced by dietary methionine supplementation (2% wt/wt in rodent chow) in a mouse model of doxorubicin-induced cardiotoxicity. Our data showed that methionine supplementation doubled serum homocysteine levels, inducing mild hyperhomocysteinaemia. Doxorubicin at a cumulative dosage of 25 mg/kg body weight led to significant weight loss and severe cardiac dysfunction, which were further exacerbated by methionine-induced mild hyperhomocysteinaemia. Doxorubicin-induced cardiac atrophy, cytoplasmic vacuolisation, myofibrillar disarray and loss, as well as cardiac fibrosis, were also exacerbated by methionine-induced mild hyperhomocysteinaemia. Additional folic acid supplementation (0.006% wt/wt) prevented methionine-induced hyperhomocysteinaemia and inhibited hyperhomocysteinaemia-aggravated cardiac dysfunction and cardiomyopathy. In particular, hyperhomocysteinaemia increased both serum and cardiac oxidative stress, which could all be inhibited by folic acid supplementation. Therefore, we demonstrated for the first time that hyperhomocysteinaemia could exacerbate doxorubicin-induced cardiotoxicity in mice, and the pathogenic effects of hyperhomocysteinaemia might at least partially correlate with increased oxidative stress and could be prevented by folic acid supplementation. Our study provides preliminary experimental evidence for the assessment of hyperhomocysteinaemia as a potential risk factor for chemotherapy-induced cardiotoxicity in cancer patients.

Association between hyperuricaemia and hand osteoarthritis: data from the Xiangya Osteoarthritis Study.

OBJECTIVE: The pathogenesis of hand osteoarthritis (OA) remains unknown. Hyperuricaemia, which is related to inflammation, may play a role in hand OA, but evidence is lacking. In a large population-based study, we examined the association between hyperuricaemia and hand OA. METHODS: Participants were from the Xiangya OA Study, a community-based observational study. Hyperuricaemia was defined as serum urate >416 µmol/L in men and >357 µmol/L in women. Radiographic hand OA (RHOA) was defined as presence of the modified Kellgren-Lawrence grade ≥2 in any hand joint. Symptomatic hand OA (SHOA) was defined as presence of both self-reported symptoms and RHOA in the same hand. The associations of hyperuricaemia with RHOA or SHOA were examined using generalised estimating equations. RESULTS: Among 3628 participants, the prevalence of RHOA was higher in participants with hyperuricaemia than those with normouricaemia (26.9% vs 20.9%), with an adjusted OR (aOR) of 1.34 (95% CI 1.11 to 1.61). The associations were consistent in men (aOR 1.33, 95% CI 1.01 to 1.74) and women (aOR 1.35, 95% CI 1.05 to 1.74). Hyperuricaemia was mainly associated with bilateral RHOA (aOR 1.54, 95% CI 1.18 to 2.01) but not unilateral RHOA (aOR 1.13, 95% CI 0.89 to 1.45). Prevalence of SHOA was higher, although statistically insignificant, in participants with hyperuricaemia (aOR 1.39, 95% CI 0.94 to 2.07). CONCLUSION: In this population-based study, hyperuricaemia was associated with a higher prevalence of hand OA. Future prospective studies are required to investigate the temporal relationship. TRIAL REGISTRATION NUMBER: NCT04033757.