Congenital joint synostosis (CJS) is a functional impairment resulting from failure in joint morphogenesis during embryonic development. Clinically, it may be classified as syndromic (sCJS) and non-syndromic (nsCJS) disorders. Common sCJS include chromosomal disorders such as Klinefelter syndrome and single-gene disorders like Apert/Pfeiffer/Crouzon syndromes, Holt-Oram syndrome, Ehlers-Danlos syndrome, and Radial-ulnar synostosis with thrombocytopenia, presenting with multiple system/organ anomalies. By contrast, nsCJS manifest with only joint abnormalities, affecting one or multiple joints. This review has focused on human nsCJS and its genetic etiology. To date, variants in seven genes (NOG, GDF5, FGF9, GDF6, FGF16, SMAD6, and MECOM) have been identified as causative factors for nsCJS. This review has focused on such genes and provided a comprehensive review for the clinical phenotypes, genetic patterns, common variants, and underlying mechanisms associated with nsCJS based on a literature review. In addition, it has also analyzed other candidate genes for nsCJS within the context of relevant signaling pathways involved in joint morphogenesis.

BACKGROUND: Step width is a spatial variable in the frontal plane, defined as the mediolateral distance between the heel (forefoot during sprinting) of bilateral feet at initial contact. Variations in step width may impact the lower limb biomechanics. This systematic review aimed to synthesize the published findings to determine the influence of acute changes in step width on locomotion biomechanics and provide implications for injury prevention and enhanced sports performance.
METHODS: Literature was identified, selected, and appraised in accordance with the methods of a systematic review. Four electronic databases (Web of Science, MEDLINE via PubMed, Scopus, and ScienceDirect) were searched up until May 2023 with the development of inclusion criteria based on the PICO model. Study quality was assessed using the Downs and Black checklist and the measured parameters were summarized.
RESULTS: Twenty-three articles and 399 participants were included in the systematic review. The average quality score of the 23 studies included was 9.39 (out of 14). Step width changed the kinematics and kinetics in the sagittal, frontal, and transverse planes of the lower limb, such as peak rearfoot eversion angle and moment, peak hip adduction angle and moment, knee flexion moment, peak knee internal rotation angle, as well as knee external rotation moment. Alteration of step width has the potential to change the stability and posture during locomotion, and evidence exists for the immediate biomechanical effects of variations in step width to alter proximal kinematics and cues to impact loading variables.
CONCLUSIONS: Short-term changes in step width during walking, running, and sprinting influenced multiple lower extremity biomechanics. Narrower step width may result in poor balance and higher impact loading on the lower extremities during walking and running and may limit an athlete\'s sprint performance. Increasing step width may be beneficial for injury rehabilitation, i.e., for patients with patellofemoral pain syndrome, iliotibial band syndrome or tibial bone stress injury. Wider steps increase the supporting base and typically enhance balance control, which in turn could reduce the risks of falling during daily activities. Altering the step width is thus proposed as a simple and non-invasive treatment method in clinical practice.

Osteoarthritis (OA) is a common arthritis types in animals that causes persistent pain and reduces quality of life. Although a high-fat diet (HFD) is widely believed to induce obesity and have adverse effects on the body, the connection between HFD and joint health is not well understood. Therefore, in this study, 32 healthy male New Zealand rabbits were randomly divided into four groups: healthy rabbits fed a standard diet (NDG, n=8) or an HFD (HDG, n=8), rabbits fed a standard diet (OAG, n=8) and an HFD (HOG, n=8), and arthritis was induced by intra-articular enzyme injection. After 12 weeks of HFD feeding, articular cartilage, synovium, and subchondral bone were isolated and collected. Joint tissue damage was evaluated using histopathological and imaging tests. The results showed that there was no significant difference in body weight between rabbits fed a normal diet and those fed an HFD. However, the HFD led to an increase in joint injuries in both induced and non-induced arthritis rabbits. Specifically, the HFD induced lipid metabolism disorders and liver damage in vivo, significantly elevating the levels of serum inflammatory cytokines and bone metabolism markers. Moreover, HFD exacerbated articular cartilage damage in the joints and increased the accumulation of inflammatory cells in synovial tissue, resulting in a notable increase in synovial macrophages and inflammatory cytokines. Additionally, HFD accelerated the bone resorption process in subchondral bone, leading to the destruction of bone mass and subchondral bone microstructure. In summary, the results of this study indicate that an HFD can cause histological damage to the articular cartilage, synovium, and subchondral bone in rabbits, exacerbating arthritis in pre-existing joint damage. Notably, weight is not the primary factor in this effect.

Mallards inhabit soft grounds such as mudflats, marshes, and beaches, demonstrating remarkable proficiency in traversing these grounds. This adeptness is closely linked to the adjustments in the operation of their hindlimbs. This study employs high-speed videography to observe postural adjustments during locomotion across mudflats. Analysis of spatiotemporal parameters of the hindlimbs reveals transient and continuous changes in joints (tarsometatarso-phalangeal joint (TMTPJ), intertarsal joint (ITJ), knee, and hip) during movement on different ground hardness and slope (horizontal and uphill). The results indicate that as the stride length of the mallard increases, its speed also increases. Additionally, the stance phase duration decreases, leading to a decrease in the duty factor. Reduced ground hardness and increased slope lead to delayed adjustment of the TMTPJ, ITJ, and knee. Mallards adjust their stride length by augmenting ITJ flexion on steeper slopes, while reduced hardness prompts a decrease in TMTPJ flexion at touch-down. Additionally, the hip undergoes two brief extensions during the stance phase, indicating its crucial role in posture adjustment and propulsion on uphill grounds. Overall, the hindlimb joints of the mallard function as a whole musculoskeletal system, with each joint employing a distinct strategy for adjusting to adapt to various ground conditions.

Oral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear. We used undenatured type II collagen in a prophylactic regime -7.33 mg/kg three times/week- to describe the mechanisms associated with protective oral immune-therapy (OIT) in gut and joint during experimental Collagen-Induced Arthritis (CIA). OIT reduced disease incidence to 50%, with reduced expression of IL-17 and IL-22 in the joints of asymptomatic mice. Moreover, whilst the gut tissue of arthritic mice shows substantial damage and activation of tissue-specific immune networks, oral administration of undenatured type II collagen protects against gut pathology in all mice, symptomatic and asymptomatic, rewiring IL-17/IL-22 networks. Furthermore, gut fucosylation and microbiome composition were also modulated. These results corroborate the relevance of the gut-joint axis in arthritis, showing novel regulatory mechanisms linked to therapeutic OIT in joint disease.

UNASSIGNED: Previous studies have revealed that Galectin-9 (Gal-9) acts as an apoptosis modulator in autoimmunity and rheumatic inflammation. In the present study, we investigated the potential role of Gal-9 as a biomarker in patients with rheumatoid arthritis (RA), especially as an indicator of functional limitations and radiographic joint damage.
UNASSIGNED: A total of 146 patients with RA and 52 age- and sex-matched healthy controls were included in this study. Clinical data including disease activity, physical function, and radiographic joint damage were assessed. Functional limitation was defined as the Stanford Health Assessment Questionnaire (HAQ) disability index >1. Subjects with joint erosion >0 or joint space narrowing >0 were considered to have radiographic joint damage. Serum Gal-9 levels were detected by an enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression analysis were used to evaluate the association between Gal-9 and high disease activity and functional limitations, and a prediction model was established to construct predictive nomograms.
UNASSIGNED: Serum levels of Gal-9 were significantly increased in patients with RA compared to those in healthy controls (median 13.1 ng/mL vs. 7.6 ng/mL). Patients with RA who were older (>65 years), had a longer disease duration (>5 years), longer morning stiffness (>60mins), elevated serum erythrocyte sedimentation rate and C-reactive protein, and difficult-to-treat RA had significantly higher Gal-9 levels than those in the corresponding control subgroups (all p <0.05). Patients with RA were divided into two subgroups according to the cut-off value of Gal-9 of 11.6 ng/mL. Patients with RA with Gal-9 >11.6 ng/mL had a significantly higher core clinical disease activity index, HAQ scores, Sharp/van der Heijde modified Sharp scores, as well as a higher percentage of advanced joint damage (all p<0.05) than patients with Gal-9 ≤11.6 ng/mL. Accordingly, patients with RA presenting either functional limitations or radiographic joint damage had significantly higher serum Gal-9 levels than those without (both p <0.05). Furthermore, multivariate logistic regression analysis showed that a serum level of Gal-9 >11.6 ng/mL was an independent risk factor for high disease activity (OR=3.138, 95% CI 1.150-8.567, p=0.026) and presence of functional limitations (OR=2.455, 95% CI 1.017-5.926, p=0.046), respectively.
UNASSIGNED: Gal-9 could be considered as a potential indicator in patients with RA, especially with respect to functional limitations and joint damage.

GABBR1 receptors have been implicated in the progression of rheumatoid arthritis (RA), and p38 MAP kinase (MAPK) was shown to be downregulated by GABA and result in unchecked production of pro-inflammatory cytokine. GABBR1 is a member of GABA receptors, and it is known to be upregulated and plays a vital role in RA. Glucocorticoids are efficient therapeutics in rheumatoid arthritis (RA) and are known to regulate GABA actions; therefore, we intended to investigate the potential of glucocorticoids in RA concerning the potential pathway GABBR1/MAPK. Joint specimens were obtained from collagen-induced arthritis mouse model. A double-blind semi-quantitative analysis of vascularity, cell infiltration, as well as lining thickness by help of a 4-point scale setting was used to assess joint inflammation. Expression of GABBR1 and p38 was evaluated immunohistochemically. In vitro peripheral blood (PB), synovial fluid (SF), and mononuclear cells (MCs) were acquired from RA mice. Western blotting was used for detecting expression of GABBR1 and p38 proteins. The presence of high levels of GABBR1 and p38 was prevalent in RA joints relative to healthy joints and related to the inflammation level. Glucocorticoid treatment alters GABBR1 along with p38 protein expression in joints while reducing joint inflammation. Ex vivo and in vitro assays revealed glucocorticoids have a direct impact on p38, such as the decreased GABBR1 expression level after dexamethasone incubation with SFMC. GABBR1 together with p38 expression in RA joints depends on local inflammation and can be targeted by glucocorticoids.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common forms of arthritis with undefined etiology and pathogenesis. Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ), which act as sensors for cellular mechanical and inflammatory cues, have been identified as crucial players in the regulation of joint homeostasis. Current studies also reveal a significant association between YAP/TAZ and the pathogenesis of OA and RA. The objective of this review is to elucidate the impact of YAP/TAZ on different joint tissues and to provide inspiration for further studying the potential therapeutic implications of YAP/TAZ on arthritis. Databases, such as PubMed, Cochran Library, and Embase, were searched for all available studies during the past two decades, with keywords \"YAP,\" \"TAZ,\" \"OA,\" and \"RA.\"

Aiming at the status of muscle and joint damage caused on surgeons keeping surgical posture for a long time, this paper designs a medical multi-position auxiliary support exoskeleton with multi-joint mechanism by analyzing the surgical postures and conducting conformational studies on different joints respectively. Then by establishing a human-machine static model, this study obtains the joint torque and joint force before and after the human body wears the exoskeleton, and calibrates the strength of the exoskeleton with finite element analysis software. The results show that the maximum stress of the exoskeleton is less than the material strength requirements, the overall deformation is small, and the structural strength of the exoskeleton meets the use requirements. Finally, in this study, subjects were selected to participate in the plantar pressure test and biomechanical simulation with the man-machine static model, and the results were analyzed in terms of plantar pressure, joint torque and joint force, muscle force and overall muscle metabolism to assess the exoskeleton support performance. The results show that the exoskeleton has better support for the whole body and can reduce the musculoskeletal burden. The exoskeleton mechanism in this study better matches the actual working needs of surgeons and provides a new paradigm for the design of medical support exoskeleton mechanism.
针对外科医生长时间保持手术姿态而造成的肌肉和关节损伤的现状，本文通过分析手术姿态，分别对不同关节进行构型研究，设计了一种具有多关节机构的医用多位姿辅助支撑外骨骼。然后通过建立人机静力学模型，本研究得到人体穿戴外骨骼前后的关节扭矩、关节力，并用有限元分析软件对外骨骼强度校核。结果表明，外骨骼最大应力小于材料强度要求，整体形变小，外骨骼结构强度满足使用需求。最后，本研究选取受试者参与足底压力试验，并结合人机静力学模型进行生物力学仿真，从足底压力、关节扭矩和关节力、肌肉力和肌肉总体代谢三个方面进行结果分析，以评估外骨骼支撑性能。结果表明，外骨骼对全身有较好的支撑性，能够减轻肌肉骨骼负担。本研究的外骨骼机构更匹配外科医生的实际工作需求，为医用支撑外骨骼机构设计提供了一种新的范例。.

In recent years, the adhesive technology has been widely used in the production of high-strength joins and precise positioning of various materials, such as metals, glass and composite materials. The adhesive technology has become a promising assembly process in the aerospace field due to its versatility, low creep and high damage tolerance. However, the reliability and predictability of adhesive bonding still require further development due to the complex operating conditions involved. Therefore, this article reviews and discusses the latest advances in aerospace adhesive technology, such as methods for improving bonding performance, bonding techniques (including joints structure and failure modes) and self-healing adhesive layers. Additionally, the current research results are summarised, and possible development trends and research directions in the field of adhesive bonding are prospected.