Promoting chondrogenesis by targeted delivery to the degenerating cartilage in early treatment of osteoarthritis.

Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.

The transformation of 20-year social participation policies of older people in China: Network analysis and text analysis.

BACKGROUND: Social participation of older adults is a crucial component of China's aged care services and an important strategy for actively addressing the aging population. Analyzing policy texts on older people's social participation can inform future policy formulation and the development of relevant programs. OBJECTIVES: This study aims to quantitatively analyze the transformation of China's social participation policies for older people from 1999 to 2023, employing institutional network analysis and policy text analysis. METHOD: A two-dimensional policy analysis framework was constructed based on the perspective of "policy tools and social participation stages." Using Rost Content Mining 6.0 and Nvivo 11.0 Plus software, 55 national-level policy texts were coded. Structural analysis of policy-issuing subjects and topic words was conducted to visualize the findings. RESULTS: The analysis revealed that the policy-issuing subjects demonstrated strong authority but weak coordination, with a lack of communication and cooperation across subjects. The use of policy tools was imbalanced, with an over-reliance on supply-type tools and insufficient use of demand-type tools. Additionally, the lack of effective policy tools to support various social participation stages has limited policy implementation. CONCLUSION: With technological advancement and changing needs of the elderly population, there is a need for a more systematic and forward-looking top-level design of elderly social participation policies: accelerating the systematization and precision of technological elements in policies for elderly social participation, integrating social organizations via technological platforms to mobilize diverse stakeholder engagement, and addressing the digital divide between the elderly and new technologies is imperative.

Ethical risks in robot health education: A qualitative study.

BACKGROUND: As health education robots may potentially become a significant support force in nursing practice in the future, it is imperative to adhere to the European Union's concept of "Responsible Research and Innovation" (RRI) and deeply reflect on the ethical risks hidden in the process of intelligent robotic health education. AIM: This study explores the perceptions of professional nursing professionals regarding the potential ethical risks associated with the clinical practice of intelligent robotic health education. RESEARCH DESIGN: This study adopts a descriptive phenomenological approach, employing Colaizzi's seven-step method for data analysis. PARTICIPANTS AND RESEARCH CONTEXT: We conducted semi-structured interviews with 17 nursing professionals from tertiary comprehensive hospitals in China. ETHICAL CONSIDERATIONS: This study has been approved by the Ethics Committee of the Second Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Provincial Second Chinese Medicine Hospital. FINDINGS: Nursing personnel, adhering to the principles of RRI and the concept of "person-centered" care, have critically reflected on the potential ethical risks inherent in robotic health education. This reflection has primarily identified six themes: (a) threats to human dignity, (b) concerns about patient safety, (c) apprehensions about privacy disclosure, (d) worries about implicit burdens, (e) concerns about responsibility attribution, and (f) expectations for social support. CONCLUSIONS: This study focuses on health education robots, which are perceived to have minimal ethical risks, and provides rich and detailed insights into the ethical risks associated with robotic health education. Even seemingly safe health education robots elicit significant concerns among professionals regarding their safety and ethics in clinical practice. As we move forward, it is essential to remain attentive to the potential negative impacts of robots and actively address them.

Long-term care for community-dwelling older adults: A systematic review of clinical practice guidelines and consensus statements.

This review identified clinical practice guidelines (CPGs) and consensus statements (CSs) that include recommendations on long-term care for community-dwelling older adults. Additionally, it assessed their quality using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool to determine high-quality guidelines and synthesis recommendations from high-quality guidelines and evaluate the quality of these guidelines using the AGREE-Recommendation Excellence (AGREE-REX) tool. A systematic search was performed (November 2023) in MEDLINE, PubMed, Guidelines International Network (GIN), National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Registered Nurses' Association of Ontario (RNAO), National Guideline Clearinghouse (NGC), and Scottish Intercollegiate Guidelines Network (SIGN). Two reviewers independently selected and assessed the articles using AGREE II. A meeting was held to appraise the quality of the guidelines (AGREE II mean score >70 %) using AGREE-REX. The analysis included 14 CPGs and 2 CSs. Of these, 7 CPGs reached the standard of >70 %, the 'Scope and purpose' domain obtained the highest score with 85.43 (± 17.87), and the 'Applicability' domain scored lowest with 46.93 (± 26.74). Regarding the score of AGREE-REX, the seven CPGs were considered as 'moderate', with the 'Clinical Applicability' domain having the highest score of 61.29 % (±10.80) and the 'Values and Preferences' domain having the lowest score of 38.14 % (±9.26). Four themes were synthesised from the seven high-quality CPGs: planning and delivering person-centred home care, cognitive impairment, and screening for impaired vision and falls. The quality of CPGs and CSs on long-term care for community-dwelling older adults has room for improvement, and higher-quality guidelines are required to meet the long-term care needs of community-dwelling older adults.

Near Infrared Responsive Gold Nanorods Attenuate Osteoarthritis Progression by Targeting TRPV1.

Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with the main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation of transient receptor potential vanilloid 1 (TRPV1) significantly alleviated cartilage degeneration by abolishing chondrocyte ferroptosis. In this work, in view of the thermal activated feature of TRPV1, Citrate-stabilized gold nanorods (Cit-AuNRs) is conjugated to TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) as a photothermal switch for TRPV1 activation in chondrocytes under near infrared (NIR) irradiation. The conjugation of TRPV1 monoclonal antibody barely affect the morphology and physicochemical properties of Cit-AuNRs. Under NIR irradiation, Cit-AuNRs@Anti-TRPV1 exhibited good biocompatibility and flexible photothermal responsiveness. Intra-articular injection of Cit-AuNRs@Anti-TRPV1 followed by NIR irradiation significantly activated TRPV1 and attenuated cartilage degradation by suppressing chondrocytes ferroptosis. The osteophyte formation and subchondral bone sclerosis are remarkably alleviated by NIR-inspired Cit-AuNRs@Anti-TRPV1. Furthermore, the activation of TRPV1 by Cit-AuNRs@Anti-TRPV1 evidently improved physical activities and alleviated pain of destabilization of the medial meniscus (DMM)-induced OA mice. The study reveals Cit-AuNRs@Anti-TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, providing a potential therapeutic strategy for the treatment of OA.

XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression.

Background: Osteoarthritis (OA) is the most common age-related musculoskeletal disease. However, there is still a lack of therapy that can modify OA progression due to the complex pathogenic mechanisms. The aim of the study was to explore the role and mechanism of XJB-5-131 inhibiting chondrocytes ferroptosis to alleviate OA progression. Methods: We treated tert-butyl hydroperoxide (TBHP)-induced ferroptosis of mouse primary chondrocytes with XJB-5-131 in vitro. The intracellular ferroptotic hallmarks, cartilage anabolic and catabolic markers, ferroptosis regulatory genes and proteins were detected. Then we established a mouse OA model via destabilization of the medial meniscus (DMM) surgery. The OA mice were treated with intra-articular injection of XJB-5-131 regularly (2 µM, 3 times per week). After 4 and 8 weeks, we performed micro-CT and histological examination to evaluate the protection role of XJB-5-131 in mouse OA subjects. RNA sequencing analysis was performed to unveil the key downstream gene of XJB-5-131 exerting the anti-ferroptotic effect in OA. Results: XJB-5-131 significantly suppressed TBHP-induced increases of ferroptotic hallmarks (ROS, lipid peroxidation, and Fe2+ accumulation), ferroptotic drivers (Ptgs2, Pgd, Tfrc, Atf3, Cdo1), while restored the expression of ferroptotic suppressors (Gpx4, Fth1). XJB-5-131 evidently promoted the expression of cartilage anabolic and decreased the expression of cartilage catabolic markers. Moreover, intra-articular injection of XJB-5-131 significantly inhibited the expression of Cox2 and Mmp13, while promoted the expression of Col2a1, Gpx4 and Fth1 in DMM-induced mouse articular cartilage. Further, we identified Pebp1 as a potential target of XJB-5-131 by RNA sequencing analysis. The anti-ferroptosis and chondroprotective effects of XJB-5-131 were significantly diminished by Locostatin, a specific antagonist of Pebp1. Conclusion: XJB-5-131 significantly protects chondrocytes from ferroptosis in TBHP-induced mouse primary chondrocytes and DMM surgery-induced OA mice model via restoring the expression of Pebp1. XJB-5-131 is a potential therapeutic drug in the management of OA progression.

Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression.

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1). Under the alternating magnetic field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient to trigger the opening and activation of TRPV1, and effectively impeded macrophagic inflammation and chondrocyte ferroptosis. This magnetothermal modulation of TRPV1 simultaneously attenuated synovitis and cartilage degeneration in mice incurred by destabilization of medial meniscus surgery, indicating the delayed OA progression. Furthermore, MNPs-TRPV1 with AMF exposure remarkably reduced knee pain sensitivity, alleviated the crippled gait, and improved spontaneous ambulatory activity performance in the mice OA model. Overall, this work provides a potential pathogenesis-based precise OA therapy with temporally and spatially magnetothermal modulation of TRPV1 in a controllable manner.

K-CapsNet: K-Nearest Neighbor Based Convolution Capsule Network for Cerenkov Luminescence Tomography Reconstruction.

Cerenkov luminescence tomography (CLT) has received significant attention as a promising imaging modality that can display the three-dimensional (3D) distribution of radioactive probes. However, the reconstruction of CLT suffers from severe ill-posed problem. It is difficult for traditional model-based method to obtain satisfactory result. Recently, deep learning-based method have shown great potential for accurate and efficient CLT reconstruction. In this study, a KNN-based convolution capsule network, named K-CapsNet, is proposed for cerenkov luminescence tomography. In K-CapsNet, the surface photon intensity is encoded in capsule form. The KNN-based convolution and K-means clustering are proposed for efficient encoding. Numerical simulation experiments have been carried out to verify the performance of K-CapsNet, and the results show that it performs superior in source localization and morphological restoration compared with existing methods.

FISTA-NET: Deep Algorithm Unrolling for Cerenkov luminescence tomography.

Cerenkov luminescence tomography (CLT) is a highly sensitive and promising imaging technique that can be used to reconstruct the three-dimensional distribution of radioactive probes in living animals. However, the accuracy of CLT reconstruction is limited by the simplified radiative transfer equation and ill-conditioned inverse problem. To address this issue, we propose a model-based deep learning network that combines the neural network with a model-based approach to enhance the performance of CLT reconstruction. The Fast Iterative Shrinkage Thresholding Algorithm (FISTA), a traditional model-based approach, is expanded into a deep network (known as FISTA-NET). Each layer in the network represents an iteration of the algorithm steps, and connecting these layers can form a deep neural network. In addition, different from the traditional FISTA, the key parameters in FISTA, such as gradient step size and threshold value, can be learned through training data without manual production. To evaluate the performance of FISTA-NET, numerical simulation experiments were conducted, which demonstrate its excellent positioning and shape recovery abilities.Clinical Relevance-This indicates that FISTA-NET strategy can significantly improve the quality of CLT reconstruction, which is further beneficial to the assessment of disease activity and treatment effect based on CLT.

The Mechanism of Peach Gum Polysaccharide Preventing UVB-Induced Skin Photoaging by Regulating Matrix Metalloproteinanse and Oxidative Factors.

Exposure to ultraviolet light can cause oxidative damage and accelerate skin aging and is one of the main causes of skin aging. Peach gum polysaccharide (PG) is a natural edible plant component that has many biological activities, such as regulating blood glucose and blood lipids and improving colitis, as well as antioxidant and anticancer properties. However, there are few reports on the antiphotoaging effect of peach gum polysaccharide. Therefore, in this paper, we study the basic composition of the raw material peach gum polysaccharide and its ability to improve UVB-induced skin photoaging damage in vivo and in vitro. The results show that peach gum polysaccharide is mainly composed of mannose, glucuronic acid, galactose, xylose, and arabinose, and its molecular weight (Mw) is 4.10 × 106 g/mol. The results of the in vitro cell experiments show that PG could significantly alleviate UVB-induced apoptosis of human skin keratinocytes, promote cell growth repair, reduce the expression of intracellular oxidative factors and matrix metal collagenase, and improve the extent of oxidative stress repair. Moreover, the results from the in vivo animal experiments showed that PG could not only effectively improve the phenotype of UVB-induced photoaged skin in model mice but also significantly improve their oxidative stress status, regulate the contents of ROS and the levels of SOD and CAT, and repair the oxidative skin damage induced by UVB in vivo. In addition, PG improved UVB-induced photoaging-mediated collagen degradation in mice by inhibiting the secretion of matrix metalloproteinases. The above results indicate that peach gum polysaccharide has the ability to repair UVB-induced photoaging and may be used as a potential drug and antioxidant functional food to resist photoaging in the future.

Evaluating the Risk of Social Isolation in Older People: AHP-Fuzzy Comprehensive Evaluation.

Background: Social isolation is a serious and pervasive health issue among older people, and it is difficult to identify and assess effectively. Based on a thorough and scientific evaluation index system, AHP-Fuzzy comprehensive evaluation could be a valuable technique. Objective: It is crucial to establish interventions that focus on risk factors for the prevention of social isolation in order to give a strong scientific foundation for enhancing older people's health habits. This can be achieved by using a fuzzy comprehensive evaluation method to assess the risk of social isolation in older people. Methods: A hundred community members over 60 from Nanjing were selected as the evaluation subjects in China. After the element layer was split into three categories of "social risk, economic risk, and cultural risk" using the analytic hierarchy process approach, a total of 22 assessment indicators were picked to develop a risk evaluation index system. Results: The risk level of social isolation belonging to the "low risk, relatively low risk, medium risk, relatively high risk, high risk" of membership degree are respectively "0.3392, 0.2632, 0.2257, 0.1069, 0.0650". Fuzzy comprehensive evaluation analysis showed that social relations (0.4934), monthly income (0.4654), health status (0.5960) were significant factors of social isolation risk in older people. The results showed that factors related to social risk had the most significant impact on social isolation. Conclusion: It is scientific and feasible to construct the risk evaluation index model of social isolation risk for the elderly by using AHP-Fuzzy comprehensive evaluation method. In preventing social isolation of older people in the future, we should pay attention to the impact of social and cultural factors on them, and provide practical intervention programs and references from the government, community, family.

Rational design, synthesis, antifungal evaluation and docking studies of antifungal peptide CGA-N12 analogues based on the target CtKRE9.

Candida tropicalis is a major non-albicans species that causes invasive candidiasis. CGA-N12, an anti-Candida peptide found by our group, disrupted cell wall architecture by inhibiting the activity of the protein killer-resistant 9 (KRE9), a ß-1,6-glucan synthase specific to Candida spp. and plants. Herein, a set of CGA-N12 analogues were rationally designed based on the interaction networks between CGA-N12 and C. tropicalis KRE9 (CtKRE9). Seven CGA-N12 analogues with significantly improved antifungal activity against C. tropicalis were screened by reducing the docking energy of CGA-N12 and CtKRE9 and increasing the number of positive charges on CGA-N12 based on a stable three-dimensional model of CtKRE9. CGA-N12 and its analogues exhibited antifungal activity against C. tropicalis and its persist cells; they also inhibited biofilm formation and eradicated preformed biofilms. Compared with fluconazole, they displayed higher activities against the growth of persister cells and more effective preformed biofilm eradication. Among them, CGA-N12-0801, CGA-N12-0902 and CGA-N12-1002 displayed much higher activity and anti-proteinase digestion stability than CGA-N12. Specifically, CGA-N12-0801 was the optimal analogue, with a minimum inhibitory concentration of 3.46 µg/mL and a therapeutic index of 158.07. The results of electronic microscopy observations and KRE9 activity inhibition assays showed that CGA-N12 and its analogues killed C. tropicalis by disrupting the architecture of the cell wall and the integrity of the cell membrane. In conclusion, for the first time, we provide a simple and reliable method for the rational design of antimicrobial peptides and ideal candidates for treating Candida infections that not effectively eliminated by azole drugs.

In utero exposure to per-/polyfluoroalkyl substances (PFASs): Preeclampsia in pregnancy and low birth weight for neonates.

Per-/polyfluoroalkyl substances (PFASs) have been linked to preeclampsia with inconsistent directions for outcomes. However, information regarding the joint effects of PFASs mixtures on preeclampsia as well as their associations with the low birth weight (LBW) and small for gestational age (SGA) is nascent. The present study included 82 women with preeclampsia and 169 healthy participants from Hangzhou, China. Fifteen PFASs were analyzed in maternal serum before delivery. PFOA and 6:2Cl-PFESA were associated with higher incidence of preeclampsia both linearly and by tertile. Each log-unit increase in serum PFOA (OR:5.29, 95% CI: 1.05, 26.7, p = 0.044) and 6:2 Cl-PFESA (OR:1.02, 95%CI: 1.00, 1.48, p = 0.045) concentrations were associated with increased risks of preeclampsia. These effects were more profound among primiparous women carrying female fetuses. Both PFOA and PFUnDA concentrations were significantly associated with higher odds of early-onset preeclampsia, but the associations tended to be null for late-onset. In addition, each logarithmic increment in PFOA concentrations were significantly associated with a 0.262 and 0.224 mmHg increase in systolic (95% CI: 0.147, 0.377) and diastolic (95% CI: 0.133, 0.314) blood pressures. Using Bayesian kernel machine regressions (BKMR), the overall effects of PFASs mixture concentrations on preeclampsia showed an increasing trend, with PFOA being the largest contributor. With regard to birth weight, the Cox proportional hazards model indicated that significantly higher risks of the LBW were associated with preeclampsia than normal pregnancy (OR: 4.56, 95% CI: 2.44, 6.68, p = 0.000). Increased LBW risks were found for the higher PFOA exposure both linearly and by tertile. Besides, serum PFOA and PFUnDA concentrations were significantly associated with higher odds of SGA development. Nevertheless 4:2 FTS and ADONA were inversely associated with LBW and SGA incidences. Further adverse birth outcomes should be explored to elucidate the health implications of PFASs exposure and preeclampsia development.

Current situation and factors influencing elderly care in community day care centers: a cross-sectional study.

Background: The latest census data show that people over 60 years of age account for about 18.7% of the total population in China, and the aging of the population has become an irreversible trend in the 21st century. This study aimed to investigate the current status and factors influencing the care of the elderly in community day care centers in order to lay the foundation for the development of better services in community day care centers. Methods: This study was a cross-sectional survey using convenience sampling in Nanjing, China. The survey instrument was the Day care and Elderly Care Service Needs Questionnaire, which included the Ability of Daily Living Assessment (ADL), the Xiao Shuiyuan Social Support Rating Scale (SSRS) and the Day care Elderly Care Service Needs Survey Form, and a general information survey. Results: A total of 450 elderly people in day care centers were surveyed. The elderly had different levels of demand for day care services, especially regarding daily care. Correlation analyses indicated that age (r = 0.619), education level (r = 0.616), source of income (r = 0.582), caregiver (r = 0.557), satisfaction with care service (r = 0.603), and degree of ADL (r = 0.629) were correlated with the need for elderly day care services (all p < 0.05). The factors influencing the demand for day care services encompassed age, education level, income source, caregiver, satisfaction with service, and ADL (all p < 0.05). Conclusion: Elderly care services in community day care centers are mainly based on daily and spiritual comfort, and the needs of the elderly are influenced by many factors. Timely nursing care policies and measures that target these factors are needed to improve elderly care.

Elastic net-based non-negative iterative three-operator splitting strategy for Cerenkov luminescence tomography.

Cerenkov luminescence tomography (CLT) provides a powerful optical molecular imaging technique for non-invasive detection and visualization of radiopharmaceuticals in living objects. However, the severe photon scattering effect causes ill-posedness of the inverse problem, and the location accuracy and shape recovery of CLT reconstruction results are unsatisfactory for clinical application. Here, to improve the reconstruction spatial location accuracy and shape recovery ability, a non-negative iterative three operator splitting (NNITOS) strategy based on elastic net (EN) regularization was proposed. NNITOS formalizes the CLT reconstruction as a non-convex optimization problem and splits it into three operators, the least square, L1/2-norm regularization, and adaptive grouping manifold learning, then iteratively solved them. After stepwise iterations, the result of NNITOS converged progressively. Meanwhile, to speed up the convergence and ensure the sparsity of the solution, shrinking the region of interest was utilized in this strategy. To verify the effectiveness of the method, numerical simulations and in vivo experiments were performed. The result of these experiments demonstrated that, compared to several methods, NNITOS can achieve superior performance in terms of location accuracy, shape recovery capability, and robustness. We hope this work can accelerate the clinical application of CLT in the future.

ABPO-TVSCAD: alternating Bregman proximity operators approach based on TVSCAD regularization for bioluminescence tomography.

Objective.Bioluminescence tomography (BLT) is a promising non-invasive optical medical imaging technique, which can visualize and quantitatively analyze the distribution of tumor cells in living tissues. However, due to the influence of photon scattering effect and ill-conditioned inverse problem, the reconstruction result is unsatisfactory. The purpose of this study is to improve the reconstruction performance of BLT.Approach.An alternating Bregman proximity operators (ABPO) method based on TVSCAD regularization is proposed for BLT reconstruction. TVSCAD combines the anisotropic total variation (TV) regularization constraints and the non-convex smoothly clipped absolute deviation (SCAD) penalty constraints, to make a trade-off between the sparsity and edge preservation of the source. ABPO approach is used to solve the TVSCAD model (ABPO-TVSCAD for short). In addition, to accelerate the convergence speed of the ABPO, we adapt the strategy of shrinking the permission source region, which further improves the performance of ABPO-TVSCAD.Main results.The results of numerical simulations andin vivoxenograft mouse experiment show that our proposed method achieved superior accuracy in spatial localization and morphological reconstruction of bioluminescent source.Significance.ABPO-TVSCAD is an effective and robust reconstruction method for BLT, and we hope that this method can promote the development of optical molecular tomography.

Single cell RNA-seq analysis identifies ferroptotic chondrocyte cluster and reveals TRPV1 as an anti-ferroptotic target in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common degenerative joint disease primarily characterized by cartilage destruction. The aim of this study was to investigate the role, molecular characteristics and potential therapeutic target of chondrocyte ferroptosis in the pathogenesis of OA. METHODS: The expression of ferroptotic hallmarks (iron and lipid peroxidation accumulation, glutathione deletion) were analyzed in paired intact and damaged cartilages from OA patients. Single cell RNA sequencing (scRNA-seq) analysis was performed on 17,638 chondrocytes to verify the presence, investigate the molecular signatures and unveil the potential therapeutic target of ferroptotic chondrocyte cluster in human OA cartilages. Destabilization of medial meniscus (DMM)-induced OA model and tert-butyl hydroperoxide (TBHP)-treated primary mouse chondrocytes and human cartilage explants were used to evaluate the protective effect of pharmacologically activated transient receptor potential vanilloid 1 (TRPV1). The downstream molecular mechanisms of TRPV1 was further investigated in glutathione peroxidase 4 (Gpx4) heterozygous genetic deletion mice (Gpx4+/-). FINDINGS: The concentrations of iron and lipid peroxidation and the expression of ferroptotic drivers in the damaged areas of human OA cartilages were significantly higher than those in the intact cartilage. scRNA-seq analysis revealed a chondrocyte cluster characterized by preferentially expressed ferroptotic hallmarks and genes, namely ferroptotic chondrocyte cluster. Comprehensive gene set variation analysis revealed TRPV1 as an anti-ferroptotic target in human OA cartilage. Pharmacological activation of TRPV1 significantly abrogated cartilage degeneration by protecting chondrocytes from ferroptosis. Mechanistically, TRPV1 promoted the expression of GPX4, and its anti-ferroptotic role was largely mitigated in the OA model of Gpx4+/- mice. INTERPRETATION: TRPV1 activation protects chondrocytes from ferroptosis and ameliorates OA progression by upregulating GPX4. FUNDING: National Key R&D Program of China (2018YFC1105904), Key Program of NSFC (81730067), National Science Foundation of China (81772335, 81941009, 81802196), Natural Science Foundation of Jiangsu Province, China (BK20180127), Jiangsu Provincial Key Medical Talent Foundation, Six Talent Peaks Project of Jiangsu Province (WSW-079).

Construction of path analysis model on related factors of social isolation in older people.

BACKGROUND: With the gradual acceleration of population ageing, social isolation in older people has increasingly become a hot topic of social concern. The reduction of valid social participation will cause older people to weaken their sense of belonging to the community and social acquisition, negatively impacting on older people's quality of life. This study is aimed to explore the main related factors affecting the social isolation of older people, so as to provide a solid scientific basis for improving the health behaviour of older people in China. METHOD: A cross-sectional study was conducted among 2267 community residents over 60 years old from four cites in Jiangsu Province, China. Perceived social support scale, Geriatric Depression Scale, Connor-Davidson Resilience Scale, Comprehensive Ability of Older People Assessment Scale and other influencing factors scales were used to investigate the current situation. Social isolation was measured with the Lubben Social Network Scale. Demographic data were evaluated using descriptive statistical analyses and relationships among study variables were determined to use a path analysis. All data were analyzed using SPSS version 22 and AMOS version 26 using T-test, analysis of variance, logistic regression analyses, and path analysis method. The test level was set at alpha = 0.05, and the difference was statistically significant at P-value <0.05. RESULTS: The results of the model test analysis indicated that the hypothesised paths were supported by data from our samples and demonstrated significance on the path coefficients (P < 0.05). Related factors in the three dimensions of social risk, economic risk and cultural risk have an impact on the social isolation of older people in the community through direct and indirect pathways, and also indirectly through the partially mediated role of depression. Overall, our hypothesised model was retained, indicating empirical support and adequate model fit indices for the theoretical model. CONCLUSION: The findings demonstrated the predictive role of related factors of social isolation in older people. In the future, we should focus on developing interventions by uniting many forces such as society, family and older people themselves to reduce social isolation among this vulnerable population and improve the quality of life of older people and promote healthy ageing.

Instrument development and validation of the comprehensive ability of older people assessment scale.

AIM: The study is aimed to develop and psychometrically test the Comprehensive Ability of Older People Assessment scale and classify the ability grades. DESIGN: A cross-sectional design was used for instrument development. METHOD: The Comprehensive Ability of Older People Assessment scale was developed by a sample of 971 older people from 4 long-term care institutions in China. The data were collected between April 2018 and March 2020. One-way analysis of variance and multiple regression analysis was used to screen scale items, while focus group interviews were used to integrate the subjective and objective items. Confirmative factor analysis and expert judgment were applied to explore construct validity. Reliability was explored through internal consistency estimation using Cronbach's alpha and homogeneity evaluation using corrected item-total correlations. Cluster analysis and discriminant analysis were used to segment the comprehensive ability assessment scores and discriminant function was established to determine the boundary value of each segment, using correlation analysis to perform reverse verification. RESULTS: Factor analysis yielded 40 items with six dimensions, including "mentation and cognitive," "perception and communication," "emotional problems," "mental and behavioural problems," "daily life and social participation," and "skin and oral status." The Cronbach's α was 0.951, while the dimensions showed Cronbach's α values ranging from 0.760-0.946. The rationality and scientificity of this scale were proved by the correlation analysis of reverse validation. CONCLUSION: The 4-grade Comprehensive Ability of Older People Assessment scale is proved to be with good validity and reliability and should be considered for institutional assessors. IMPACT: Assessors can accurately evaluate older people's health status and nursing needs through this scale in long-term care institutions, communities and hospitals, so as to provide accurate and high-quality nursing services. It will become a scientific basis for the government to offer accurate pension subsidies, purchase pension services scientifically for older people and establish third-party objective evaluation and supervision.

Prognosis of lung cancer associated with cystic airspaces: A propensity score matching analysis.

OBJECTIVE: The association between the morphological characteristics and survival outcome of lung cancer associated with cystic airspaces (LCCAs) is unclear due to rarity of this disease. The current study attempted to compare the survival outcome between LCCAs and non-LCCAs and investigate the correlation between imaging features and prognosis of LCCA. METHOD: Of 10,835 patients diagnosed with non-small cell lung carcinoma (NSCLC) between January 2015 and December 2016, 123 patients with LCCA were included. The non-LCCA group comprised 3136 patients with primary solitary adenocarcinoma or squamous cell lung cancer. Propensity score matching (PSM) was performed for age, sex, tumor size, tumor stage, and lymph node involvement in a 1:1 ratio between the LCCAs and non-LCCAs, and the correlation between radiological features and recurrence-free survival (RFS) was analyzed. RESULT: The computed tomography (CT) lesion size was found to be higher in all LCCA subtypes, particularly in Type III (a cystic airspace with a mural nodule) and Type IV (mixed) LCCAs (3.09 and 3.65 cm, respectively), than in non-LCCAs (2 cm) after PSM. Three-year RFS in the LCCA group was higher than in the non-LCCA group (Type I- IV LCCAs: 100%, 84%, 77% and 83%, respectively vs. non-LCCAs: 77%). However, statistically significant difference was only found in comparison between LCCA Type I (thin-walled) and non-LCCA groups (P = 0.026). Type III lung cancer exhibited the worst survival among all four LCCA subtypes. CONCLUSIONS: The CT lesion size and pathologic tumor size varied significantly across LCCAs. Type I LCCAs exhibited better survival than non-LCCAs, whereas Type III LCCAs exhibited the worst survival rate among the four LCCA subtypes.