Factors associated with the core dimensions of spiritual health among older adults with chronic obstructive pulmonary disease: A cross-sectional study.

AIMS: To investigate the level of spiritual health in older patients with chronic obstructive pulmonary disease (COPD) from the core dimensions and to explore its associated factors. DESIGN: A cross-sectional study. METHODS: Participants were recruited from four hospitals between September 2020 and June 2021, using a convenience sampling. Older patients with COPD (n = 162) completed the demographic and disease-related information questionnaires, Function Assessment of Chronic Illness Therapy Spiritual Scale, 10-item Connor-Davidson Resilience Scale, General Self-efficacy Scale, Social Support Rating Scale, COPD Assessment Test, 15-item Geriatric Depression Scale and modified Medical Research Council Dyspnea Scale. Descriptive statistics, Pearson and Spearman correlation analyses, t-tests, one-way ANOVA and multiple linear regression models were used. RESULTS: Older patients with COPD have a moderate level of spiritual health. The multiple linear regression analysis showed that psychological resilience, general self-efficacy, social support, symptom burden and monthly income were associated with the core dimensions of spiritual health. CONCLUSION: Chinese older patients with COPD have a moderate level of spiritual health. Psychological resilience, general self-efficacy, social support, monthly income and symptom burden were associated with the core dimensions of spiritual health. IMPACT: This study is the first to investigate the level of spiritual health in older patients with COPD from the core dimensions and to explore its associated factors, providing a basis for developing spiritual intervention programs. Our findings can help us realize that intervention strategies of psychological resilience, general self-efficacy and social support can all be used to enhance spiritual health. Nurses should focus on the spiritual health of older COPD patients with high symptom burden and low monthly income. PATIENT OR PUBLIC CONTRIBUTION: Although we did not directly involve patients and the public because of the COVID-19 pandemic, the results of the study will be disseminated to patients and the public through WeChat and seminars.

Fall risk perception in older adults: A concept analysis.

BACKGROUND: Fall prevention is crucial for older adults. Enhanced fall risk perception can encourage older adults to participate in fall prevention programs. However, there is still no unified definition of the concept of fall risk perception. OBJECTIVE: To explore the concept of fall risk perception in older adults. DESIGN: A concept analysis. DATA SOURCES: The literature was searched using online databases including PubMed, Cochrane Library, Embase, CINAHL Complete, PsycINFO, Web of Science, China National Knowledge Infrastructure, WangFang and SinoMed. Searches were also conducted in Chinese and English dictionaries. The literature dates from the establishment of the database to April 2023. METHODS: The methods of Walker and Avant were used to identify antecedents, attributes and consequences of the concept of "fall risk perception" in older adults. RESULTS: Eighteen publications were included eventually. The attributes were identified as: (1) dynamic change, with features of continuum and stage; (2) whether falls are taken seriously; (3) a self-assessment of the fall probability, which is driven by individual independence; and (4) involves multiple complex emotional responses. The antecedents were identified as: (1) demographic and disease factors; (2) psychological factors and (3) environmental factors. The consequences were identified as: (1) risk-taking behaviour; (2) risk compensation behaviour; (3) risk transfer behaviour; and (4) emotions. CONCLUSION: A theoretical definition of fall risk perception was identified. A conceptual model was developed to demonstrate the theoretical relationships between antecedents, attributes and consequences. This is helpful for the development of relevant theories and the formulation of fall prevention measures based on fall risk perception as the intervention target.

Factors Associated with the e-Health Literacy Among Older Adults with Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

Background: The telemanagement model in chronic diseases needs older patients to have a certain level of e-Health literacy. According to Electronic Health Literacy model, factors associated with the e-Health literacy among older patients could be comprehensively investigated from individual, situational, and environmental aspects. Objectives: To investigate the e-Health literacy levels among older patients with chronic obstructive pulmonary disease (COPD) and explore associated factors. Methods: A cross-sectional study was conducted among older patients with COPD. The e-Health Literacy Scale was used to measure individuals' e-Health literacy. The multiple linear regression was applied to identify factors associated with e-Health literacy. Results: A total of 230 responses were included in the final analysis. The average score of e-Health literacy for older COPD patients was 24.66 (6.86). After adjusting the model, the results of multiple linear regression demonstrated that aging attitudes (B = 0.067, p < 0.001), technophobia (B = -0.285, p < 0.001), and self-efficacy (B = 0.431, p < 0.001) accounted for 68.3% (p < 0.001) of the total variation in e-Health literacy. Conclusion: This study identifies significant correlations of technophobia, aging attitudes, and self-efficacy, respectively, with e-Health literacy, and self-efficacy and technophobia may be constant predictive factors of e-Health literacy. In the future, intervention research on e-Health literacy should be conducted from a social psychology perspective, with particular emphasis on addressing negative aging attitudes and technophobia. That will promote the tele-management model of chronic diseases. Trial Registration: Chinese Clinical Trial Registry (ChiCTR): ChiCTR1900028563; http://apps.who.int/trialsearch/default.aspx.

Patients' and healthcare providers' perceptions and experiences of telehealth use and online health information use in chronic disease management for older patients with chronic obstructive pulmonary disease: a qualitative study.

BACKGROUND: Telehealth and online health information provide patients with increased access to healthcare services and health information in chronic disease management of older patients with chronic diseases, addressing the challenge of inadequate health resources and promoting active and informed participation of older patients in chronic disease management. There are few qualitative studies on the application of telehealth and online health information to chronic disease management in older patients. Chronic obstructive pulmonary disease is one of the most common chronic diseases in older adults. Telehealth is widely used in the management of chronic obstructive pulmonary disease. The purpose of this study was to explore the perceptions and experiences of older patients and healthcare providers in the application of telehealth and online health information to chronic disease management of chronic obstructive pulmonary disease. METHODS: A qualitative descriptive study with data generated from 52 individual semi-structured interviews with 29 patients [Law of the People's Republic of China on the protection of the rights and interests of older people (2018 Revised Version) = >60 years old] with chronic obstructive pulmonary disease and 23 healthcare providers. The inductive thematic analysis method was used for data analysis. RESULTS: Four themes and 16 sub-themes were identified in this study. Four themes included: faced with a vast amount of online health information, essential competencies and personality traits ensuring older patients' participation and sustained use, user experience with the use of technology, being in a complex social context. CONCLUSION: The ability of patients to understand health information should be fully considered while facilitating access to online health information for older patients. The role of health responsibility and user experience in older patients' participation and sustained use of telehealth and online health information needs to be emphasised. In addition, the complex social context is a determining factor to be considered, particularly the complex impact of a reliance on offspring and social prejudice on the behaviour of older adults using telehealth and online health information.

Effectiveness of comprehensive geriatric assessment intervention on quality of life, caregiver burden and length of hospital stay: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Comprehensive geriatric assessment (CGA) interventions can improve functional ability and reduce mortality in older adults, but the effectiveness of CGA intervention on the quality of life, caregiver burden, and length of hospital stay remains unclear. The study aimed to determine the effectiveness of CGA intervention on the quality of life, length of hospital stay, and caregiver burden in older adults by conducting meta-analyses of randomised controlled trials (RCTs). METHODS: A literature search in PubMed, Embase, and Cochrane Library was conducted for papers published before February 29, 2020, based on inclusion criteria. Standardised mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CIs) was calculated using the random-effects model. Subgroup analyses, sensitivity analyses, and publication bias analyses were also conducted. RESULTS: A total of 28 RCTs were included. Overall, the intervention components common in different CGA intervention models were interdisciplinary assessments and team meetings. Meta-analyses showed that CGA interventions improved the quality of life of older people (SMD = 0.12; 95% CI = 0.03 to 0.21; P = 0.009) compared to usual care, and subgroup analyses showed that CGA interventions improved the quality of life only in participants' age > 80 years and at follow-up ≤3 months. The change value of quality of life in the CGA intervention group was better than that in the usual care group on six dimensions of the 36-Item Short-Form Health Survey questionnaire (SF-36). Also, compared to usual care, the CGA intervention reduced the caregiver burden (SMD = - 0.56; 95% CI = - 0.97 to - 0.15, P = 0.007), but had no significant effect on the length of hospital stay. CONCLUSIONS: CGA intervention was effective in improving the quality of life and reducing caregiver burden, but did not affect the length of hospital stay. It is recommended that future studies apply the SF-36 to evaluate the impact of CGA interventions on the quality of life and provide supportive strategies for caregivers as an essential part of the CGA intervention, to find additional benefits of CGA interventions.

Perceptions and experiences of older patients and healthcare professionals regarding shared decision-making in pulmonary rehabilitation: A qualitative study.

OBJECTIVE: To understand the perceptions and experiences of older patients with chronic obstructive pulmonary disease (COPD) and healthcare professionals (HCPs) regarding shared decision-making in pulmonary rehabilitation (PR). DESIGN: A qualitative study using single, semi-structured interviews, and thematic analysis. SETTING: Face-to-face interviews were conducted in the Jiangnan University, in hospital and in patients' homes. PARTICIPANTS: Twenty-two older patients with COPD and 29 HCPs. METHODS: An initial codebook and semi-structured interview guide were developed based on the shared decision-making 3-circle conceptual model. Thematic analysis was used to analyze data. RESULTS: The study identified 10 themes that describe the perceptions and experiences of patients and HCPs involved in PR decision-making: (1) patients' confidence, (2) patients' perceptions of the cost-benefit of decisions, (3) patients' perceived stress about the consequences of decision-making, (4) HCPs' perceived stress on shared decision-making, (5) cognitive biases of patients toward illness and rehabilitation, (6) shared decision-making as a knowledge gap, (7) the knowledge gap between patients and HCPs, (8) authority effect, (9) family support, (10) human resources. These themes were then divided into three groups according to their characteristics: (1) the feelings of the participants, (2) knowledge barriers, and (3) support from the social system. CONCLUSION: Patients and HCPs described their negative perceptions and experiences of participating in decision-making in PR. The implementation of shared decision-making in PR is currently limited; therefore, health education for patients and families should be strengthened and a training system for HCPs in shared decision-making should be established.

Optical axis-driven field discontinuity in a hyperbolic medium.

The altering permittivity tensor of a hyperbolic medium from diagonal to off-diagonal by the constructive manipulation of the optical axis (also called tilted hyperbolic medium) has attracted much interest recently. Here, the electromagnetic field solutions of waves interacting with a tilted hyperbolic medium are established. Detailed calculations reveal that when a transverse magnetic (TM) polarized wave is incident from a tilted hyperbolic medium to a dielectric medium, tangential components of electric fields are expected to be discontinuous at the interface. Extraordinary surface voltages are induced at the inner boundary of the tilted hyperbolic medium, which prevents the reflection of electromagnetic waves. This alternative behavior of induced extraordinary surface voltages enriches the understanding of continuity across the boundary and provides a novel perspective for their realizations among multiple experimental platforms.

Evaluating an Intervention Program Using WeChat for Patients With Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial.

BACKGROUND: The application of telemedicine in home pulmonary rehabilitation interventions for the management of patients with chronic obstructive pulmonary disease (COPD) has achieved promising results. OBJECTIVE: This study aimed to develop a WeChat official account (Pulmonary Internet Explorer Rehabilitation [PeR]) based on social media. It further evaluated the effect of PeR on the quality of life, symptoms, and exercise self-efficacy of patients with COPD. METHODS: The functional modules of PeR were developed by a multidisciplinary team according to the electronic health-enhanced chronic care model (eCCM) components. A total of 106 patients were randomly selected (53 in the PeR group and 53 in the outpatient face-to-face group [FtF]). Pulmonary rehabilitation intervention was conducted for 3 months, and the outcome was observed for 3 months. The primary outcome was patient quality of life measured with the COPD assessment test (CAT). The secondary outcomes were evaluated using the modified Medical Research Council scale (mMRC), exercise self-regulatory efficacy scale (Ex-SRES), and St George's Respiratory Questionnaire (SGRQ). RESULTS: The intention-to-treat analysis was used in the study. A total of 94 participants completed the 6-month pulmonary rehabilitation program. No statistically significant differences were observed in CAT (F1,3=7.78, P=.001), Ex-SRES (F1,3=21.91, P<.001), and mMRC scores (F1,3=29.64, P<.001) between the two groups with the variation in time tendency. The Ex-SRES score had a significant effect on the CAT score (P=.03). The partial regression coefficient of Ex-SRES to CAT was 0.81, and Exp (B) was 2.24. CONCLUSIONS: The telemedicine technology was effective using the eCCM combined with a behavioral intervention strategy centering on self-efficacy. Pulmonary rehabilitation at home through PeR and FtF could improve the sense of self-efficacy and quality of life and alleviate symptoms in patients with COPD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022770; https://tinyurl.com/tmmvpq3.

Effectiveness of Telemedicine Intervention for Chronic Obstructive Pulmonary Disease in China: A Systematic Review and Meta-Analysis.

Background: Telemedicine market in China has been rapidly developing. However, no systematic review has been published in China. Details of the implementation of telemedicine interventions in the chronic obstructive pulmonary disease (COPD) in China have not been described, and the effectiveness of telemedicine interventions is still unclear. Therefore, in this review, we describe the implementation details of telemedicine intervention in China and access the efficacy of telemedicine. Materials and Methods: A literature search was conducted in Embase, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), Wan Fang Data, and China Science and Technology Journal Database by July 9, 2018. Results: A total number of 24 studies were meta-analyzed. There are many differences during the implementation of telemedicine in China. Quality of life in the group of the telemedicine intervention was better than that in the control group (mean difference = -4.93 [95% confidence interval; CI -6.86 to -3.01], p < 0.00001), but the heterogeneity is high (I2 = 86%, p = 0.0001). The rates of hospitalization were lower than those in the control group (odds ratio = 0.24 [95% CI 0.20-0.29], p < 0.00001), and the heterogeneity was low (I2 = 25%, p = 0.14). Conclusion: The implementation of telemedicine in China has not yet been standardized. Nonetheless, results of our review indicated that telemedicine in China can improve the quality of life and reduce the rates of hospitalization in COPD patients.

Harnessing graphene-hBN hyperstructure for single-photon sources.

One of the key challenges to move single-photon sources into practical applications is the ability to efficiently extract light from a single quantum emitter while maintaining efficient photon emission. Here, we propose to harness the optical topological transitions of graphene-hBN hyperstructure to engineer the emission from quantum emitters and achieve preferential power extraction. We have designed a hyperstructure, which possesses tunability of spontaneous emission and enhancement of extraction during optical topological transitions from the closed (ellipsoid) isofrequency surface to an open (hyperboloid) isofrequency surface by tuning the chemical potential of graphene. Such an interesting feature relies exclusively on the hyperbolic properties of hBN and tunable behavior of graphene, which is confirmed by detailed calculations and simulations. Remarkably, single-photon sources based on the hyperstructure do not require overmuch microfabrication and they are capable of working at tunable frequency.

Broadband surface-wave transformation cloak.

Guiding surface electromagnetic waves around disorder without disturbing the wave amplitude or phase is in great demand for modern photonic and plasmonic devices, but is fundamentally difficult to realize because light momentum must be conserved in a scattering event. A partial realization has been achieved by exploiting topological electromagnetic surface states, but this approach is limited to narrow-band light transmission and subject to phase disturbances in the presence of disorder. Recent advances in transformation optics apply principles of general relativity to curve the space for light, allowing one to match the momentum and phase of light around any disorder as if that disorder were not there. This feature has been exploited in the development of invisibility cloaks. An ideal invisibility cloak, however, would require the phase velocity of light being guided around the cloaked object to exceed the vacuum speed of light--a feat potentially achievable only over an extremely narrow band. In this work, we theoretically and experimentally show that the bottlenecks encountered in previous studies can be overcome. We introduce a class of cloaks capable of remarkable broadband surface electromagnetic waves guidance around ultrasharp corners and bumps with no perceptible changes in amplitude and phase. These cloaks consist of specifically designed nonmagnetic metamaterials and achieve nearly ideal transmission efficiency over a broadband frequency range from 0(+) to 6 GHz. This work provides strong support for the application of transformation optics to plasmonic circuits and could pave the way toward high-performance, large-scale integrated photonic circuits.

Transient response of a signal through a dispersive invisibility cloak.

The transient response of the invisibility cloak has long been an interesting research topic, since it is valuable to further understand the steady-state process and to design more effective cloaks. Here we investigate the transient response of a set of dispersive invisibility cloaks impinged on by a sinusoidal signal or a modulated Gaussian pulse using the finite difference time domain method. Cylindrical cloaks with linear, convex, and concave transformation functions are studied. We find that their time to reach a steady state is different and they grow significantly when the thickness of the cloak decreases. Moreover, a centrally depressed ladder-like spatial time delay distribution is observed with a modulated Gaussian pulse. We show that the central frequency of the Gaussian pulse suffers a blue-shift in the forward scattering direction in agreement with previous theoretical predictions.

Experience of Older Patients with COPD Using Disease Management Apps: A Qualitative Study.

(1) Background: Digital medicine is developing in the management of chronic diseases in older people, but there is still a lack of information on the use of disease management apps in older patients with COPD. This study aims to explore the views and experience of older patients with COPD on disease management apps to provide a basis for the development and promotion of apps for geriatric diseases. (2) Methods: A descriptive qualitative research method was used. Older patients with COPD (N = 32) with experience using disease management apps participated in semi-structured interviews. Thematic analysis was used to analyze the data. (3) Results: Seven themes were defined: (a) feeling curious and worried when facing disease management apps for the first time; (b) actively overcoming barriers to use; (c) gradually becoming independent by continuous online learning; (d) feeling safe in the virtual environment; (e) gradually feeling new value in online interactions; (f) relying on disease management apps under long-term use; (g) expecting disease management apps to meet personalized needs. (4) Conclusions: The adoption and use of disease management apps by older people is a gradual process of acceptance, and they can obtain a wide range of benefits in health and life.

Molybdenum nanoparticles as a potential topical medication for alopecia treatment through antioxidant pathways that differ from minoxidil.

BACKGROUND: Hair loss is a common dermatological condition including various types such as alopecia areata, androgenetic alopecia, etc. Minoxidil is a topical medication used for treating hair loss, which is effective for various types of alopecia. However, minoxidil has limitations in treating hair loss, such as slow onset of action and low efficacy, and it cannot effectively inhibit one of the major pathogenic factors of hair loss - excessive oxidative stress. METHODS: Transition metal elements with rapid electron transfer, such as molybdenum, have been extensively studied and applied for inhibiting oxidative stress. We established a mouse model for hair growth and intervened with nano-sized molybdenum, minoxidil, and a combination of both. The physicochemical properties of nano-sized molybdenum enabled it to mediate oxidative stress more quickly. RESULTS: The results showed that nano-sized molybdenum can accelerate hair growth, increase the number of local hair follicles, and reduce the expression of oxidative stress-related molecules such as iNOS, COX2, and androgen receptors. The combination of nano-sized molybdenum and minoxidil showed an additive effect in promoting hair growth. CONCLUSION: Our findings suggest that nano-sized molybdenum might be a potential topical medication for treating hair loss by inhibiting the oxidative stress pathway. Nano-sized molybdenum, alone or in combination with minoxidil, could be a promising therapeutic approach for patients with hair loss, particularly those who do not respond well to current treatments. Further clinical studies are warranted to confirm the efficacy and safety of this novel treatment.

Patient Experiences and Perspectives of Their Decision-Making to Accept Lung Transplantation Referral: A Qualitative Study.

Providing early lung transplantation referral services should be considered to reduce pre-transplant mortality in patients with advanced disease. This study aimed to explore the reasons for lung transplantation referral decisions in patients and provide evidence for the development of transplantation referral services. This was a qualitative, retrospective, and descriptive study involving conventional content analysis. Patients in evaluation, listing, and post-transplant stages were interviewed. A total of 35 participants (25 male and 10 female) were interviewed. Four main themes were defined: (1) expectations for lung transplantation leading to the decision (a gamble for a silver lining, a return to normal life, and occupation); (2) facing uncertain outcomes (personal luck arranging everything; belief in success; incidents leading to "It's decided then"; hesitation when making a decision due to fear); (3) facing various information from peers, doctors, and so on; (4) complex policy and societal support (providing transplantation referral services earlier, family attachment and oral approval responses contribute to the referral decision, and so on). The findings of this study might enrich existing referral services, including training for family members and healthcare providers, a checklist and package of critical events in the patient lung transplantation referral decision-making process, precision services based on behavioral personas, and a curriculum to enhance patient decision self-efficacy.

Effectiveness of patient decision aid supported shared decision-making intervention in in-person and virtual hybrid pulmonary rehabilitation in older adults with chronic obstructive pulmonary disease: A pilot randomized controlled trial.

INTRODUCTION: Tele-pulmonary rehabilitation is increasingly advocated but cannot completely substitute for in-person services for chronic conditions. Adherence to Pulmonary rehabilitation (PR) remains low in chronic obstructive pulmonary disease (COPD) patients. Shared decision-making (SDM) promotes patients' participation in PR decisions and helps patients and healthcare providers to jointly make decisions that patients are informed and aligned with patient preferences and values, which are critical for patient adherence to PR. OBJECTIVE: This study aimed to develop a hybrid in-person and virtual model of home-based PR services for older COPD patients and study the effectiveness of the patient decision aid (PDA)-supported recurring SDM intervention on patient adherence to PR, rehabilitation outcomes, and decision-related outcomes, as well as to explore the mechanisms of the intervention on PR adherence. METHODS: A total of 78 older COPD patients were randomly assigned to the PR group (n = 39) or PDA-PR group (n = 39). Both groups were conducted hybrid in-person and virtual PR intervention for 3 months. The primary outcomes were patients' quality of life and PR adherence. The secondary outcomes were dyspnea symptoms, exercise self-efficacy, knowledge, and decision-related outcomes. RESULTS: A total of 72 participants completed the 3-month PR program. There were statistically significant differences in PR adherence (p = 0.033), COPD assessment test (CAT) scores (p = 0.016), PR knowledge (p < 0.001), decision self-efficacy (p < 0.001), decision conflict (p < 0.001), and decision regret scores (p = 0.027) between the two groups. The modified Medical Research Council Dyspnoea scale (mMRC) score was significantly decreased only in PDA-PR group (p = 0.011). No statistically significant differences were observed in St George's Respiratory Questionnaire (SGRQ) score (p = 0.078), Exercise Self-Regulatory Efficacy Scale (Ex-SRES) score (p = 0.29) and COPD knowledge (p = 0.086) between the two groups. PR value score had a significant effect on adherence to PR (p = 0.007) and CAT score (p = 0.028). CONCLUSIONS: PDA supported recurring SDM intervention was helpful in maintaining older COPD patients' PR adherence and had advantages in improving quality of life, enhancing PR knowledge, decision self-efficacy, and reducing decision conflict and decision regret, but did not improve SGRQ and Ex-SRES. PR value score influenced patients' rehabilitation adherence and quality of life. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR1900028563; http://apps.who.int/trialsearch/default.aspx.

Histone demethylase KDM5B licenses macrophage-mediated inflammatory responses by repressing Nfkbia transcription.

Macrophages play a critical role in the immune homeostasis and host defense against invading pathogens. However, uncontrolled activation of inflammatory macrophages leads to tissue injury and even fuels autoimmunity. Hence the molecular mechanisms underlying macrophage activation need to be further elucidated. The effects of epigenetic modifications on the function of immune cells draw increasing attention. Here, we demonstrated that lysine-specific demethylase 5B (KDM5B), a classical transcriptional repressor in stem cell development and cancer, was required for the full activation of NF-κB signaling cascade and pro-inflammatory cytokine production in macrophages. KDM5B deficiency or inhibitor treatment protected mice from immunologic injury in both collagen-induced arthritis (CIA) model and endotoxin shock model. Genome-wide analysis of KDM5B-binding peaks identified that KDM5B was selectively recruited to the promoter of Nfkbia, the gene encoding IκBα, in activated macrophages. KDM5B mediated the H3K4me3 modification erasing and decreased chromatin accessibility of Nfkbia gene locus, coordinating the elaborate suppression of IκBα expression and the enhanced NF-κB-mediated macrophage activation. Our finding identifies the indispensable role of KDM5B in macrophage-mediated inflammatory responses and provides a candidate therapeutic target for autoimmune and inflammatory disorders.

Targeting KAT2A inhibits inflammatory macrophage activation and rheumatoid arthritis through epigenetic and metabolic reprogramming.

Epigenetic regulation of inflammatory macrophages governs inflammation initiation and resolution in the pathogenesis of rheumatoid arthritis (RA). Nevertheless, the mechanisms underlying macrophage-mediated arthritis injuries remain largely obscure. Here, we found that increased expression of lysine acetyltransferase 2A (KAT2A) in synovial tissues was closely correlated with inflammatory joint immunopathology in both RA patients and experimental arthritis mice. Administration of MB-3, the KAT2A-specific chemical inhibitor, significantly ameliorated the synovitis and bone destruction in collagen-induced arthritis model. Both pharmacological inhibition and siRNA silencing of KAT2A, not only suppressed innate stimuli-triggered proinflammatory gene (such as Il1b and Nlrp3) transcription but also impaired NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in vivo and in vitro. Mechanistically, KAT2A facilitated macrophage glycolysis reprogramming through suppressing nuclear factor-erythroid 2-related factor 2 (NRF2) activity as well as downstream antioxidant molecules, which supported histone 3 lysine 9 acetylation (H3K9ac) and limited NRF2-mediated transcriptional repression of proinflammatory genes. Our study proves that acetyltransferase KAT2A licenses metabolic and epigenetic reprogramming for NLRP3 inflammasome activation in inflammatory macrophages, thereby targeting KAT2A represents a potential therapeutic approach for patients suffering from RA and relevant inflammatory diseases.

Development of a Pulmonary Rehabilitation Patient Decision Aid for Patients with Chronic Obstructive Pulmonary Disease: Mixed Methods Study.

Background: Pulmonary rehabilitation is an important part of the management of chronic obstructive pulmonary disease (COPD), but the participation rate of pulmonary rehabilitation in COPD patients is low. Patient decision aids can facilitate patient participation in pulmonary rehabilitation decisions by providing information and incorporating patient values. The aim of this study was to develop a pulmonary rehabilitation decision aid for patients with COPD. Objective: The aim of this study was to develop a WeChat-based pulmonary rehabilitation patient decision aid to help older patients with COPD participate in pulmonary rehabilitation decision-making. Methods: We developed the decision aid in 3 stages: (1) a literature review was performed to determine the evidence for pulmonary rehabilitation options and outcomes for patients with COPD. (2) a semi-structured interview study was conducted to develop and iterate patient decision aids. (3) usability, acceptability and language expression testing in patients and healthcare professionals. Results: A total of 16 randomized controlled studies were included in the literature review. Thirty-six participants received semi-structured interviews. The results of interview include four themes: key points of age-friendly design, content of the tool, presentation requirements of contents and study evidence of the tool and other views and suggestions. The resultant goals-of-care decision aid achieved good usability and acceptability. The frequency of language expression increased in both patients and healthcare professionals. Conclusion: This study uses a systematic development process to develop the first pulmonary rehabilitation decision aid for patients with COPD. It has good usability, acceptability and increased communication between patients and healthcare professionals in the pulmonary rehabilitation decision-making process. Trial Registration: Chinese Clinical Trial Registry (ChiCTR): ChiCTR1900028563; http://apps.who.int/trialsearch/default.aspx.

Loss of BTK ameliorates the pathological cardiac fibrosis and dysfunction.

Cardiac fibrosis is a common irreversible pathological feature of diverse heart disorders. Uncontrolled cardiac fibrosis contributes to maladaptive cardiac remodeling and eventually heart failure. However, the molecular determinants of ischemic and non-ischemic pathological cardiac fibrosis remain largely unknown. Here, we investigated the role of Bruton's tyrosine kinase (BTK) in cardiac fibrosis and remodeling of mice under various pathological conditions. BTK expression was increased in myocardium of mice after pressure overload or myocardial infarction (MI). BTK was mainly located in cardiac fibroblasts of myocardium, and its expression in isolated cardiac fibroblasts was also upregulated following TGF-ß treatment. The deficiency or pharmacological inhibition of BTK with the second-generation inhibitor Acalabrutinib attenuated cardiac fibrosis, preserved cardiac function and prevented adverse cardiac remodeling, which protected against heart failure in mice following pressure overload or MI. BTK deficiency or inhibitor treatment significantly decreased the expression of pro-fibrotic molecules in isolated cardiac fibroblasts and inhibited the transition of fibroblasts to myofibroblasts in response to diverse pathological stresses. BTK directly bound and phosphorylated TGF-ß receptor Ⅰ (TßRⅠ) at tyrosine 182, and then promoted the activation of downstream SMAD-dependent or -independent TGF-ß signaling, leading to the enhanced transition of fibroblasts to pro-fibrotic myofibroblasts and the excessive extracellular matrix gene expression. Our finding uncovers a driving role of BTK in cardiac fibrosis and dysfunction following pressure overload and MI stress, and highlights novel pathogenic mechanisms in ischemic and non-ischemic maladaptive cardiac remodeling, which presents as a promising target for the development of anti-fibrotic therapy.