Chronic Disease Research Articles

Agonist antibody to MuSK protects mice from MuSK myasthenia gravis

Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to muscle weakness. In the most common forms of autoimmune MG, antibodies attack components of the postsynaptic membrane, including the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). MuSK, a master regulator of NMJ development, associates with the low-density lipoprotein-related receptor 4 (Lrp4) to form the signaling receptor for neuronal Agrin, a nerve-derived synaptic organizer. Pathogenic antibodies to MuSK interfere with binding between MuSK and Lrp4, inhibiting the differentiation and maintenance of the NMJ. MuSK MG can be debilitating and refractory to treatments that are effective for AChR MG. We show here that recombinant antibodies, derived from MuSK MG patients, cause severe neuromuscular disease in mice. The disease can be prevented by a MuSK agonist antibody, presented either prophylactically or after disease onset. These findings suggest a therapeutic alternative to generalized immunosuppression for treating MuSK MG by selectively and directly targeting the disease mechanism.

Epidemiology of myasthenia gravis in Denmark, Finland and Sweden: a population-based observational study

BackgroundIncidence and prevalence rates of myasthenia gravis (MG) vary considerably across studies, and mortality risk is rarely addressed. We examined the prevalence and incidence rates, mortality and factors associated with...

Geniposidic Acid Attenuates Chronic Tubulointerstitial Nephropathy Through Regulation of the NF-ƙB/Nrf2 Pathway Via Aryl Hydrocarbon Receptor Signaling.

Renal fibrosis is an outcome of chronic kidney disease, independent of the underlying etiology. Renal fibrosis is caused primarily by oxidative stress and inflammation. We identified the components of Plantaginis semen and elucidated their anti-fibrotic and anti-inflammatory mechanisms. The renoprotective components and underlying molecular mechanisms of P. semen were investigated in rats with adenine-induced chronic tubulointerstitial nephropathy (TIN) and in idole-3-acetic acid (IAA)-stimulated NRK-52E cells. Acetate and n-butanol extracts were found to be the bioactive fractions of P. semen. A total of 65 compounds including geniposidic acid (GPA), apigenin (APG), and acteoside (ATS) were isolated and identified. Among the seven main extract components, treatment with GPA, APG, and ATS reduced the serum levels of creatinine and urea in TIN rats. Mechanistically, GPA ameliorated renal fibrosis through repressing aryl hydrocarbon receptor (AHR) signaling and regulating redox signaling including inhibiting proinflammatory nuclear factor kappa B (NF-ƙB) and its target gene products as well as activated antioxidative nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream target gene products in both TIN rats and IAA-stimulated NRK-52E cells. The inhibitory effect of GPA on AHR, NF-Ƙb, and Nrf2 signaling were partially abolished in IAA-stimulated NRK-52E cells treated with CH223191 compared with untreated IAA-stimulated NRK-52E cells. These data demonstrated that GPA alleviates oxidative stress and inflammation partly by suppressing AHR signaling.

Exosomes derived from hypoxic alveolar epithelial cells promote the phenotypic transformation of pulmonary artery smooth muscle cells via the Rap1 pathway

Background: Hypoxic pulmonary hypertension (HPH) is one of the important pathophysiological changes in chronic pulmonary heart disease. Hypoxia promotes the phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs). Extracellular exosomes regulate vascular smooth muscle cell (VSMC) phenotypic switch. Aim: Given the importance of exosomes and alveolar epithelial cells (AECs) in HPH, the present study aimed to address the issue of whether AEC-derived exosomes promote HPH by triggering PASMC phenotypic switch. Methods: Cell Counting Kit-8 (CCK-8), TRITC-phalloidin staining, and Western blotting were used to examine the effects of AEC-derived exosomes on cell proliferation, intracellular actin backbone distribution, and expression of phenotypic marker proteins in PASMCs. Transcriptomics sequencing was used to analyze differentially expressed genes (DEGs) between groups. Results: Hypoxia-induced exosomes (H-exos) could promote the proliferation of PASMCs, cause the reduction of cellular actin microfilaments, promote the expression of synthetic marker proteins (ELN and OPN), reduce the expression of contractile phenotypic marker proteins (SM22-α and α-SMA), and induce the phenotypic transformation of PASMCs. Transcriptomics sequencing analysis showed that the Rap1 signaling pathway was involved in the phenotypic transformation of PASMCs induced by H-exos. Conclusion: The present study identified that hypoxia-induced AEC-derived exosomes promote the phenotypic transformation of PASMCs and its mechanism is related to the Rap1 signaling pathway.

Treatment adherence priorities: Results of an online survey of doctors providing outpatient services

BACKGROUND: The opinion of doctors regarding the current issue of low patient adherence to modern medicine will help identify weaknesses in the system and methods to improve them. AIM: To assess the doctors’ opinion regarding the problem of adherence to outpatient treatments. MATERIALS AND METHODS: Using an online survey form (nine questions regarding adherence to outpatient treatments), 105 doctors were surveyed, including general practitioners (GPs; 51%), therapists (27%), cardiologists (21%), and other specialties (1%). The survey results were processed using hierarchical cluster analysis. RESULTS: The following clusters were identified: cluster 1 (K1), which included 62 respondents (GPs, 63% and therapists, 32%); and cluster 2 (K2), which included 43 respondents (cardiologists, 47%; and GPs, 35%). Doctors in both the clusters correctly determined the adherence to treatment (K1=77%, K2=88%; p=0.531), followed clinical practice guidelines when diagnosing a patient with cardiovascular disease (K1=66%, K2=88%; p=0.020), believed that the doctor’s behavior influences the patient’s adherence (K1=86%, K2=98%; p=0.045), and believed that patients should be educated regarding their disease (K1=84%, K2=100%, p=0.005). They believed that the most significant topics to be taught were arterial hypertension, heart failure (HF), coronary artery disease, arrhythmia, and chronic kidney disease (K1=81%, K2=86%; p=0.876). Furthermore, they agreed that the use of technology and mobile apps (K1=61%, K2=70%, p=0.371) could increase patient adherence to treatment. Twenty doctors correctly identified the medications indicated for HF with reduced ejection fraction to improve patient prognosis (K1=2, K2=18; p 0.001). The remaining respondents answered partially correctly (K1=97%, K2=58%; p 0.001). The respondents identified that the lack of time at appointments to explain and improve the patient’s motivation for treatment (K1=47%, K2=47%, p=0.226) and the patient’s low health literacy (K1=26%, K2=35%; p=0.226) were the most significant reasons for low adherence. CONCLUSION: Most physicians providing outpatient services are aware of the concept of medication adherence and following clinical practice guidelines when managing patients with cardiovascular pathology. The lack of sufficient time for outpatient appointments and the patient’s low health literacy are the leading factors of low adherence to treatment. Thus, the doctors unanimously believe that educating patients regarding their disease will increase adherence to treatment.

Safety of remdesivir in the treatment of acute SARS-CoV-2 infection in pediatric patients

BackgroundTransaminase and creatinine elevations have been well described in adults treated with remdesivir for COVID-19. It is hypothesized that a similar safety profile exists in children with COVID-19 treated with remdesivir, but available data are limited, especially in children < 12 months. The primary aim of this study was to determine the prevalence and timing of elevations in transaminases and creatinine in children with COVID-19 who were treated with remdesivir.MethodsThis was a retrospective, observational cohort study including all pediatric patients admitted to a single, freestanding children’s hospital who were positive for COVID-19 and received at least 1 dose of remdesivir between 1/1/2020 and 5/31/2022. Available baseline and peak transaminase and creatinine concentrations were evaluated. Multivariable logistic regression analysis was performed to identify risk factors for transaminase elevation.ResultsA total of 180 patients met inclusion criteria. Creatinine elevation of any grade was noted in 16% and remained elevated only in those with underlying chronic kidney disease. Transaminase elevation of any grade was noted in 58% of patients and remained elevated in only 1%. Older age and critical respiratory disease were associated with higher risk of significant transaminase elevation, whereas non-Hispanic ethnicity was strongly associated with protection against significant transaminase elevation.ConclusionsIn our cohort of hospitalized children with COVID-19 who were treated with remdesivir, most patients experienced only mild transaminitis and normal creatinine concentrations. A limited number of patients experienced laboratory abnormalities which were transient, suggesting a favorable safety profile for remdesivir use in pediatrics.

Beyond the organ: lung microbiome shapes transplant indications and outcomes.

The lung microbiome plays a crucial role in the development of chronic lung diseases, which may ultimately lead to the need for lung transplantation. Also, perioperative results seem to be connected with altered lung microbiomes and its dynamic changes providing a possible target for optimizing short-term outcome after transplantation. A literature review using MEDLINE, PubMed Central and Bookshelf was performed. Chronic lung allograft dysfunction (CLAD) seems to be influenced and partly triggered by changes in the pulmonary microbiome and dysbiosis, e.g. through increased bacterial load or abundance of specific species such as Pseudomonas aeruginosa. Additionally, the specific indications for transplantation, with their very heterogeneous changes and influences on the pulmonary microbiome, influence long term outcome.Next to composition and measurable bacterial load, dynamic changes in the allografts microbiome also possess the ability to alter long-term outcomes negatively. This review discusses the "new" microbiome after transplantation and the associations with direct postoperative outcome. With the knowledge of these principles the impact of alterations in the pulmonary microbiome in hindsight to CLAD and possible therapeutic implications are described and discussed. The aim of this review is to summarize the current literature regarding pre- and postoperative lung microbiomes and how they influence different lung diseases on their progression to failure of conservative treatment. This review provides a summary of current literature for centers looking for further options in optimizing lung transplant outcomes and highlights possible areas for further research activities investigating the pulmonary microbiome in connection to transplantation.

Forest Therapy as an Alternative and Sustainable Rehabilitation Practice: A Patient Group Attitude Investigation

The objective of this research is to investigate the awareness and opinions concerning forest therapy within a public health institution, specifically as a green prescription for patients with stable chronic disease. Through qualitative preliminary analysis, this study compared the responses of a group to gather physical activity and wood frequentation insights, as well as forest therapy patients’ attitudes. The results underline a general predisposition among respondents to engage in moderate physical activity and visit natural environments for relaxation purposes. Emerging parallelly is how forest therapy is largely an unknown practice, although it draws considerable interest and a general predisposition to participate. This research outlines the ideal conditions that emerge for participating in forest therapy sessions, including the availability to pay, pointing toward environmentally and socio-economically sustainable reflections. Further studies should extend this preliminary investigation using appropriate statistical methodologies on larger samples, involving different regions and medical conditions.

Cluster B personality disorders and psychotropic medications: a focused analysis of trends and patterns across sex and age groups.

This study investigated sex and age differences in patterns of psychotropic medication use before and after the initial diagnosis of Cluster B personality disorders (PDs) and analyzed trends over time. Analyzing data from the Quebec Integrated Chronic Disease Surveillance System for individuals newly diagnosed with Cluster B PD (≥ 14 years) between 2002 and 2018 and under the provincial public drug plan, we calculated yearly and monthly proportions of individuals exposed to psychotropic medications during the year before and after their diagnosis by sex and age. Robust Poisson regression models assessed the association between sex and exposure to psychotropic medications after the diagnosis of Cluster B PD. Among 87,778 individuals with a first Cluster B PD diagnosis (mean age: 44.5 years; 57.5% women), the proportion of users increased post-diagnosis. Notably, after diagnosis, females were more likely to receive psychiatric medications (between 78.9% and 83.7% during the study period vs. 72.8% and 76.8%). Males were less likely than females to receive antidepressants (adjusted prevalence ratio (aPR): 0.83; 99% confidence interval (CI): 0.82-0.85) and anxiolytics (aPR: 0.86; 99%CI: 0.84-0.88), whereas they had higher exposure to antipsychotics (aPR: 1.04; 99%CI: 1.02-1.06) and ADHD medications (aPR: 1.14; 99%CI: 1.07-1.2). Age-specific trends showed increased ADHD medication use among younger patients (14-24 years), and anxiolytic use predominated in those aged ≥ 65 years. Psychotropic medication use was high among Cluster B PD patients, with differences in medication classes according to age and sex. The marked sex and age differences in psychotropic medication use among Cluster B PD patients underscore the need for a sex-sensitive and age-specific approach in psychiatric care.

Unlocking the Door for Precision Medicine in Rare Conditions: Structural and Functional Consequences of Missense ACVR1 Variants.

Rare diseases and conditions have thus far received relatively less attention in the field of precision/personalized medicine than common chronic diseases. There is a dire need for orphan drug discovery and therapeutics in ways that are informed by the precision/personalized medicine scholarship. Moreover, people with rare conditions, when considered collectively across diseases worldwide, impact many communities. In this overarching context, Activin A Receptor Type 1 (ACVR1) is a transmembrane kinase from the transforming growth factor-β superfamily and plays a critical role in modulating the bone morphogenetic protein signaling. Missense variants of the ACVR1 gene result in modifications in structure and function and, by extension, abnormalities and have been predominantly linked with two rare conditions: fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. We report here an extensive bioinformatic analyses assessing the pool of 50,951 variants and forecast seven highly destabilizing mutations (R206H, G356D, R258S, G328W, G328E, R375P, and R202I) that can significantly alter the structure and function of the native protein. Protein-protein interaction and ConSurf analyses revealed the crucial interactions and localization of highly deleterious mutations in highly conserved domains that may impact the binding and functioning of the protein. cBioPortal, CanSAR Black, and existing literature affirmed the association of these destabilizing mutations with posterior fossa ependymoma, uterine corpus carcinoma, and pediatric brain cancer. The current findings suggest these deleterious nonsynonymous single nucleotide polymorphisms as potential candidates for future functional annotations and validations associated with rare conditions, further aiding the development of precision medicine in rare diseases.

Epigenetic Pathways Linking Fetal Development to Metabolic Syndrome: Mechanisms and Implications

This review explores the intricate connections between early developmental environments, epigenetic mechanisms, and long-term health outcomes. The concept of fetal programming highlights how maternal stress, nutrition, and other environmental factors during embryonic and fetal development can induce physiological changes with persistent effects extending into adulthood and across generations. Evidence suggests that these early life exposures can lead to complex diseases such as cardiovascular conditions, diabetes, and metabolic syndrome. The role of epigenetic modifications—particularly DNA methylation and histone modifications—is emphasized as a crucial mechanism through which environmental factors influence gene expression and disease susceptibility. Additionally, this review discusses the significance of sex-specific epigenetic marks and their impact on disease risk, illustrating how sex chromosomes and fluctuating sex hormones contribute to sexual dimorphism in disease prevalence. The need for further research is underscored, with a focus on understanding the factors that shape fetal growth trajectories, the mechanisms by which nutrients and hormones alter gene expression, and the barriers to healthy eating among women. Addressing these issues is vital for reducing chronic disease prevalence and improving public health across generations.

A review on advancements in emerging processing of whey protein: Enhancing functional and nutritional properties for functional food applications

AbstractWhey protein (WP) isolates are widely used in food products because they improve protein content, functional properties, and health benefits. It has been observed that WP can form conjugates with essential micronutrients, improving their dietary delivery and biological availability. WP and its derived bioactive peptides have potential health benefits in preventing chronic diseases. However, the off‐flavor and bitter peptides of WP are limiting factors that can be used in the food and beverage industries. Emerging innovative processing technologies, such as high hydrostatic pressure, ultrasonication, and extrusion, improve WP gelling ability, gel strength, and storage stability, providing high‐quality and healthy functional products. The integration of technological advancements into WP‐loaded fortified food products (FFPs) has increased the uptake rate of bioactive compounds, resulting in increased bioavailability and bioaccessibility in the human body. Furthermore, WP‐based FFPs treated with advanced thermal and nonthermal processing techniques possess better rheological properties, expansion ratios, and textural properties. Therefore, WP would be a promising and sustainable ingredient for developing stable functional foods. This review explores recent advancements in the processing technologies of WP, emphasizing their role in enhancing its bioavailability and functional properties for different food applications.

Views and perspectives toward implementing the Global Spine Care Initiative (GSCI) model of care, and related spine care program by the people in Cross Lake, Northern Manitoba, Canada: a qualitative study using the Theoretical Domain Framework (TDF)

BackgroundBack pain is very common and a leading cause of disability worldwide. Due to health care system inequalities, Indigenous communities have a disproportionately higher prevalence of injury and acute and chronic diseases compared to the general Canadian population. Indigenous communities, particularly in northern Canada, have limited access to evidence-based spine care. Strategies established in collaboration with Indigenous peoples are needed to address unmet healthcare needs, including spine care (chiropractic and movement program) services. This study aimed to understand the views and perspectives of Cross Lake community leaders and clinicians working at Cross Lake Nursing Station (CLNS) in northern Manitoba regarding the implementation of the Global Spine Care Initiative (GSCI) model of spine care (MoC) and related implementation strategies.MethodA qualitative exploratory design using an interpretivist paradigm was used. Twenty community partners were invited to participate in semi-structured interviews underpinned by the Theoretical Domains Framework (TDF) adapted to capture pertinent information. Data were analyzed deductively and inductively, and the interpretation of findings were explored in consultation with community members and partners.ResultsCommunity leaders (n = 9) and physicians, nurses, and allied health workers (n = 11) emphasized: 1) the importance of contextualizing the MoC (triaging and care pathway) and proposed new services through in-person community engagement; 2) the need and desire for local non-pharmacological spine care approaches; and 3) streamlining patient triage and CLNS workflow. Recommendations for the streamlining included reducing managerial/administrative duties, educating new incoming clinicians, incorporating follow-up appointments for spine pain patients, and establishing an electronic medical record system along with a patient portal. Suggestions regarding how to sustain the new spine care services included providing transportation, protecting allocated clinic space, resolving insurance coverage discrepancies, addressing misconceptions about chiropractic care, instilling the value of physical activity for self-care and pain relief, and a short-term (30-day) incentivised movement program which considers a variety of movement options and offers a social component after each session.ConclusionCommunity partners were favorable to the inclusion of a refined GSCI MoC. Adapting the TDF to unique Indigenous needs may help understand how best to implement the MoC in communities with similar needs.

Microfiltered red-purple pitaya concentrate: A promising multifunctional food-derived colorant.

Red pitaya fruit has become a source of natural colorant, because it is rich in betalains, a pigment that imparts a red-purple color that intereststhefood and cosmetics industries. This fruit also possesses high nutritional value, with a range of bioactive compounds known to confer potential health benefits and prevent chronic diseases, such as diabetes, which makes it useful for use as pharmaceutical agents and dietary supplements. In order to improve its technological and biological effects, a concentration will be required. Thus, the microfiltration, followed by vacuum concentration, can be an interesting strategy for this purpose. This study aimed to explore tangential microfiltration to produce microfiltered material, which is an important step to obtain the microfiltered red-purple pitaya concentrate. Therefore, physicochemical and chemical characterization (including 1H NMR analysis) and biological properties (toxicity and diabetes) of this concentrate were assessed, using adult zebrafish as a model. The results show that microfiltration was carried out efficiently, with an average consumption of 95.75±3.13 and 74.12±3.58kW h m-3, varying according to the material used ("unpeeled pitaya pulp" or "pitaya pulp with peel," respectively). The in vivo tests indicated non-toxicity and hypoglycemic effect of the concentrate, since the blood glucose levels were significantly lower in the zebrafish groups treated with this concentrate in comparison with that of control group. Thus, this study suggests the potential of microfiltered red-purple pitaya concentrate as a promising multifunctional food-derived colorant, exhibiting beneficial biological effects far beyond its attractive color. PRACTICAL APPLICATION: Hylocereus polyrhizus(F.A.C. Weber) Britton & Rose has attracted attention as a potential source of natural colorants because of its red-purple skin and flesh color. In addition, this fruit has a range of bioactive compounds, which make it a valuable resource for providing potential health benefits and preventing chronic diseases such as diabetes. In this paper, the microfiltered red-purple pitaya concentrate showed beneficial biological effects far beyond its attractive color. Thus, this product can be considered a promising multifunctional food-derived colorant to use in the food, pharmaceutical, or cosmetics industries.

A Closed-Loop Nanosystem Based on Piezoelectric Sensor and Pd-Nanoshell Photothermal Ablation for Renal Denervation to Treat Hypertension.

Renal sympathetic nerves play a crucial role in the pathogenesis of hypertension, and renal denervation (RDN) is a new solution for patients with refractory hypertension. However, current RDN techniques show inconsistent results in clinical application probably owing to incomplete endovascular ablation of the sympathetic nerves and a lack of measures to localize and assess efficacy. In this study, a closed-loop RDN system consisting of a sensing unit with a piezoelectric thin-film sensor (PTFS) and a treatment unit with a hollow Pd nanoparticle shell (PdNPS) with a diameter of 202.0nm for photothermal neural ablation is constructed. The PTFS can monitor and collect arterial pulsation and blood pressure (BP) and direct PdNPS to maximize RDN. PdNPS maintains a local temperature of 58-62°C under near-infrared-II irradiation (1,064nm) to achieve effective RDN within a range of 90-120s treatment window. Photothermal ablation significantly inhibits the activities of renal sympathetic nerves post-procedure and after one month and reduces the elevation of BP by > 50%. The novel closed-loop system enables safe and efficient targeting, dynamic monitoring, and ablation of the renal sympathetic nerves. This closed-loop system provides a new strategy for RDN technology and even for treating sympathetic nerve-related chronic diseases.

The critical role of cardiorespiratory fitness in disease prevention.

Cardiorespiratory fitness (CRF) has been increasingly recognized in recent years as an important predictor of risk for adverse outcomes in numerous chronic conditions. In fact, a growing body of epidemiological and clinical evidence demonstrates that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, hyperlipidemia, and type 2 diabetes. Moreover, adding CRF to these traditional risk factors significantly improves the reclassification of risk for adverse outcomes. The utility of CRF now extends far beyond all-cause and cardiovascular mortality to include the prevention and treatment of numerous other chronic conditions; CRF has been demonstrated to have a mitigating influence in as many as 40 such conditions. Herein we discuss the impact of CRF in the prevention of chronic disease in both adults and children. This discussion includes recent data on interactions between CRF and aging, obesity, statin use, incidence of diabetes, and the impact of CRF and physical activity patterns in adolescents including mental health, scholastic achievement, and cardiometabolic health. Finally, we discuss how CRF, as an essential vital sign, can be implemented in clinical practice.

Fatigue in chronic physical diseases

The term fatigue is used to describe states of unusual tiredness and exhaustion that can occur in connection with various chronic diseases, particularly cancer, multiple sclerosis, Parkinson's disease and rheumatoid arthritis. In contrast to states of exhaustion in healthy people, fatigue is characterized by the fact that it can last for long periods, is disproportionate to previous activities and does not subside after recovery phases. Fatigue is described as amultidimensional problem that encompasses physical, emotional and cognitive aspects and is associated with ahigh level of subjective suffering. Depending on the severity and course of the symptoms, fatigue is associated with aseverely reduced quality of life and it impairs participation and coping with everyday life. It also makes professional reintegration and reemployment more difficult. Although we cannot yet fully explain the aetiology and pathogenesis, fatigue in physical illnesses must be understood based on amultifactorial biopsychosocial model. The possibilities of diagnostics and an overview of various measures for clarifying fatigue are presented. The challenges for medical care are also outlined and advice is given on how to deal with them in everyday clinical practice.

ASNR Statement on Gadolinium-Based Contrast Agent Use in Patients with Chronic Kidney Disease.

Beginning in 2006, neuroradiologists became increasingly aware of the risk of nephrogenic system fibrosis (NSF) when patients suffering from chronic kidney disease (CKD) received gadolinium-based contrast agents (GBCAs) in conjunction with MRI scans. Radiology practices began withholding GBCAs from MRI patients with substantial CKD and instated a variety of safety measures to ensure that these individuals did not inadvertently receive GBCAs. As a result, the worldwide incidence of NSF was dramatically reduced. Since that time, a wealth of research on NSF and its etiology has found few unconfounded cases associated with those GBCAs categorized as Group II agents by the American College of Radiology. In 2023 and 2024, members of the American Society of Neuroradiology (ASNR) Standards and Guidelines Committee reviewed new research evidence on GBCA safety and its relevance to current MRI contrast administration guidelines for patients with CKD. This focused on systematic reviews and meta-analyses conducted during the past five years. Upon consideration of this literature, recommendations for administration of GBCAs to patients with CKD were formulated. For neuroimaging applications, the ASNR recommends that Group II GBCAs no longer be withheld in patients with CKD when these agents are medically indicated for diagnosis. Moreover, if Group II GBCAs are exclusively used in an MRI practice, other safety measures such as checking renal function or querying patients about chronic kidney disease can be discontinued. ACR = American College of Radiology; ASNR = American Society of Neuroradiology; CKD = chronic kidney disease; GBCA = gadolinium-based contrast agent; NSF = nephrogenic systemic fibrosis.

Fritillaria cirrhosa D. Don Alleviates Inflammatory Progression and Suppresses M1 Polarization of Macrophages in Chronic Obstructive Pulmonary Disease

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive and largely irreversible disease. Current therapeutic approaches for COPD are limited in terms of slowing disease progression and suppressing pulmonary inflammation. Therefore, this study aimed to identify a method for alleviating inflammation in COPD. Methods: A COPD-like mouse model was established and treated with or without Fritillaria cirrhosa D. Don (hereinafter referred to as Fritillaria). The expression levels of inflammatory cytokines in mouse serum were detected by using enzyme-linked immunosorbent assay (ELISA). Additionally, lung tissue was analyzed by hematoxylin-eosin staining and immunohistochemistry analysis, respectively. MLE-12 cells were exposed to cigarette smoke extract (CSE) and treated with or without Fritillaria. The MTT assay was conducted to assess cell viability. The activation of NF-κB p65 was determined by Western blotting (WB). Finally, flow cytometry was applied to analyze the M1 macrophage percentage. Results: The results displayed that Fritillaria downregulated the levels of IL-1β, IL-6, IL-8, and TNF-α in the COPD-like mouse serum and MLE-12 cells. Fritillaria alleviated the inflammatory response in lung tissue of COPD-like mice. The cell viability of MLE-12 cells considerably decreased when exposed to CSE, which could be restored by adding Fritillaria. The Fritillaria reduced the activation of the pro-inflammatory factor NF-κB p65 and inhibited M1 polarization of macrophages, thereby mitigating the inflammatory response. Conclusion: In conclusion, Fritillaria exhibits beneficial effects in suppressing pulmonary infection-related inflammation in both the COPD-like mouse model and in vitro cell experiments.

Predictive value of diaphragm ultrasound for mechanical ventilation outcome in patients with acute exacerbation of chronic obstructive pulmonary disease.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is often combined with respiratory failure, which increases the patient's morbidity and mortality. Diaphragm ultrasound (DUS) has developed rapidly in the field of critical care in recent years. Studies with DUS monitoring diaphragm-related rapid shallow breathing index have demonstrated important results in guiding intensive care unit patients out of the ventilator. Early prediction of the indications for withdrawal of non-invasive ventilator and early evaluation of patients to avoid or reduce disease progression are very important. To explore the predictive value of DUS indexes for non-invasive ventilation outcome in patients with AECOPD. Ninety-four patients with AECOPD who received mechanical ventilation in our hospital from January 2022 to December 2023 were retrospectively analyzed, and they were divided into a successful ventilation group (68 cases) and a failed ventilation group (26 cases) according to the outcome of ventilation. The clinical data of patients with successful and failed noninvasive ventilation were compared, and the independent predictors of noninvasive ventilation outcomes in AECOPD patients were identified by multivariate logistic regression analysis. There were no significant differences in gender, age, body mass index, complications, systolic pressure, heart rate, mean arterial pressure, respiratory rate, oxygen saturation, partial pressure of oxygen, oxygenation index, or time of inspiration between patients with successful and failed mechanical ventilation (P > 0.05). The patients with successful noninvasive ventilation had shorter hospital stays and lower partial pressure of carbon dioxide (PaCO2) than those with failed treatment, while potential of hydrogen (pH), diaphragm thickening fraction (DTF), diaphragm activity, and diaphragm movement time were significantly higher than those with failed treatment (P < 0.05). pH [odds ratio (OR) = 0.005, P < 0.05], PaCO2 (OR = 0.430, P < 0.05), and DTF (OR = 0.570, P < 0.05) were identified to be independent factors influencing the outcome of mechanical ventilation in AECOPD patients. The DUS index DTF can better predict the outcome of non-invasive ventilation in AECOPD patients.