Mitochondrial homeostasis plays a crucial role in the pathogenesis of osteoarthritis (OA), a chronic musculoskeletal disorder characterized by articular cartilage degeneration and chondrocyte apoptosis. However, molecular mechanisms underlying the association between mitophagy and OA remain unclear. Here, we aimed to investigate the role of the autophagy receptor protein optineurin (OPTN) in OA, and explore the effects of dietary intervention on OA symptoms and its relationship with OPTN-mediated mitophagy. Our findings showed the downregulation of OPTN in patients with OA. Using an Optn-knockout mouse model, we demonstrated that OPTN deficiency leads to impaired mitophagy, resulting in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and chondrocyte apoptosis. Furthermore, fasting prevented OA progression by activating OPTN-mediated mitophagy and maintaining mitochondrial homeostasis in mice. The present study revealed a novel mechanism by which OPTN-mediated mitophagy influences chondrocytes and the OA phenotype in Optn-knockout mice, suggesting that OPTN-mediated mitophagy plays a crucial role in OA development and progression. This study provides new insights into the pathogenesis of OA and offers a potential avenue for the development of novel drugs targeting OPTN to mitigate OA progression.

This study presents the development of a deep learning-based two-stage network designed for the efficient and precise segmentation of the femur in full lower limb CT images. The proposed network incorporates a dual-phase approach: rapid delineation of regions of interest followed by semantic segmentation of the femur. The experimental dataset comprises 100 samples obtained from a hospital, partitioned into 85 for training, 8 for validation, and 7 for testing. In the first stage, the model achieves an average Intersection over Union of 0.9671 and a mean Average Precision of 0.9656, effectively delineating the femoral region with high accuracy. During the second stage, the network attains an average Dice coefficient of 0.953, sensitivity of 0.965, specificity of 0.998, and pixel accuracy of 0.996, ensuring precise segmentation of the femur. When compared to the single-stage SegResNet architecture, the proposed two-stage model demonstrates faster convergence during training, reduced inference times, higher segmentation accuracy, and overall superior performance. Comparative evaluations against the TransUnet model further highlight the network’s notable advantages in accuracy and robustness. In summary, the proposed two-stage network offers an efficient, accurate, and autonomous solution for femur segmentation in large-scale and complex medical imaging datasets. Requiring relatively modest training and computational resources, the model exhibits significant potential for scalability and clinical applicability, making it a valuable tool for advancing femoral image segmentation and supporting diagnostic workflows.

Background: Rheumatoid arthritis (RA) is a globally prevalent chronic inflammatory disease. Environmental exposures, such as air pollution and smoking, are considered potential risk factors. However, the causal relationships and underlying mechanisms between these factors and RA are not fully understood. Methods: This study utilized large-scale genome-wide association studies (GWASs) from European ethnic backgrounds and employed bidirectional two-sample Mendelian randomization (MR) to investigate the relationships between air pollution, smoking, and RA. Genetic correlations were assessed using linkage disequilibrium score regression (LDSC). Furthermore, mediation analysis was conducted to evaluate the potential mediating roles of iron metabolism and urinary biomarkers in these relationships. Results: The MR analysis revealed that genetically predicted lifetime smoking intensity was associated with an 85% increased risk of RA. Subgroup analysis differentiating between seropositive RA (SPRA) and seronegative RA (SNRA) showed a causal association with SPRA, but not with SNRA. C-reactive protein was identified as a mediator in the relationship between lifetime smoking and both RA and SPRA, mediating 18.23% and 32.45% of the effects, respectively. Genetic correlation analysis further confirmed a positive genetic association between smoking and both RA and SPRA. Conclusions: This study provides significant insights into the genetic and causal connections between air pollution, smoking, and the development of RA, highlighting the mediating role of C-reactive protein. These findings not only offer new perspectives on how smoking might enhance RA risk through inflammatory pathways but also underscore the importance of reducing smoking exposure in public health strategies.

The avascular nature of articular cartilage severely limits its ability to self-repair after injury, which poses a challenge for clinical treatment, and tissue engineering aims to address this issue with scaffold-based strategies. However, the defining characteristics of an optimal scaffold remain controversial. In this study, we prepared two types of decellularized wharton's jelly (dWJ) scaffolds by trypsin combined with repeated freeze-thawing (TFT) and nuclease combined with repeated freeze-thawing (NFT), respectively. The scaffolds were tested with general characterization, decellularization effect, extracellular matrix (ECM) composition and structure retention, mechanical properties, biocompatibility, in vivo and in vitro chondrogenic effects, and in vitro anti-angiogenic effects. The results showed that the TFT-dWJ scaffolds possessed higher pore size, porosity, and swelling rate, but their Young's modulus was lower than that of the NFT-dWJ scaffolds. Both scaffolds were generally similar in terms of degradation rates. In comparison, the native ECM structure and the major components of collagen and glycosaminoglycans were better preserved in NFT-dWJ scaffolds. Importantly, dWJ scaffolds showed favorable biocompatibility and markedly promoted the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro, and accelerated cartilage damage repair in vivo. This was particularly evident with NFT-dWJ. Secondly, the dWJ scaffolds exhibited the capability to inhibit localized angiogenesis in human umbilical vein endothelial cells (HUVECs), a property that could be advantageous for preserving avascularity throughout the cartilage regeneration process. This study presents an ECM-derived scaffold fabrication strategy that optimally preserves matrix composition and microstructure, offering a promising solution for cartilage regeneration.

Rationale: Lower extremity venous ulcers are highly prevalent in elderly populations. These chronic wounds often persist for extended periods, heal poorly, and frequently recur, severely compromising patients’ quality of life while creating considerable socioeconomic burdens. When complicated by deep vein thrombosis, they further restrict viable treatment options. Patient concerns: A 55-year-old man had experienced left lower extremity varicose veins for 3 months, accompanied by a recurrent 3 × 4 cm fascial-penetrating ulcer, chronic pain, superficial venous dilation, and cutaneous hyperpigmentation. Doppler ultrasound revealed left lower extremity deep vein thrombosis. Diagnoses: The clinical evaluation confirmed primary diagnoses of left lower limb varicose veins (Clinical–Etiology–Anatomy–Pathophysiology-6 classification) and left peripheral-type deep venous thrombosis in the lower extremity. Interventions: The first surgery involves stripping and ligation of the superficial varicose veins at the ulcer site, in conjunction with tibial periosteum distraction. After 14 days of periosteal distraction, the distraction device was surgically removed in the second procedure. Outcomes: Postoperatively, the patient experienced substantial symptom relief in the affected lower extremity. Within 1 month, the ulcer formed a scab and approached healing by one and a half months. Throughout the 9-month follow-up, there was no recurrence of the ulcers, and the patient's quality of life markedly improved. Lessons: In patients with Clinical–Etiology–Anatomy–Pathophysiology-6 varicose veins complicated by deep vein thrombosis, the combination of tibial periosteum distraction with conventional stripping and ligation of superficial varicose veins resulted in symptomatic relief, promoted ulcer healing, reduced economic burden, and improved quality of life.

Vascular Intestinal Disorder (VID) significantly impacts the global disease burden, with notable regional variations in incidence, prevalence, and Disability-Adjusted Life-Years (DALYs). While high-income countries have seen a decline in VID burden due to improved healthcare, lower-income regions continue to face rising VID rates. Understanding these trends is essential for developing effective health policies and interventions. This study aimed to analyze the global trends in VID incidence, prevalence, and DALYs from 1990 to 2021. We utilized data from the global burden of disease study to calculate age-standardized rates for incidence, prevalence, and DALYs of VID from 1990 to 2021. Joinpoint regression analysis was performed to assess trend changes over time. An age-period-cohort analysis explored the impact of age, period, and birth cohort on VID burden. Decomposition, inequality, and frontier analyses were conducted to investigate the contributions of aging, population growth, and epidemiological changes to the VID burden. Overall, the global trends of VID incidence, prevalence, and DALYs showed a decline over the past 3 decades. However, regional disparities were evident. High and upper-middle socio-demographic index (SDI) regions saw significant declines in both incidence and prevalence, while low and lower-middle SDI regions experienced increases. DALYs showed a decreasing trend in most regions, though certain areas, including Central Asia and Eastern Europe, demonstrated increases. The age-period-cohort analysis revealed that age is a significant determinant of VID burden, with incidence, prevalence, and DALYs increasing with age. Population growth and aging were found to be the main drivers of increased VID burden, while epidemiological changes contributed to a global reduction in VID burden. Inequality analysis showed persistent disparities, with low-SDI regions bearing a disproportionate share of the VID burden. Policymakers must focus on addressing health inequalities and ensuring equitable distribution of global health interventions. Future research should investigate the specific causes and subtypes of VID, and improve global health data monitoring to better predict and manage shifts in disease burden.