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Medicine Jun 2024Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic... (Observational Study)
Observational Study
Elevated neutrophil-to-lymphocyte ratio combined with decreased lymphocyte-to-monocyte ratio is associated with increased peripheral airway resistance in patients with hepatic steatosis.
Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Neutrophils; Lymphocytes; Monocytes; Airway Resistance; Fatty Liver; Adult; Aged; Leukocyte Count; Lymphocyte Count
PubMed: 38941417
DOI: 10.1097/MD.0000000000038530 -
PloS One 2024Art v4.01 is a well-known profilin protein belonging to the pan-allergens group and is commonly involved in triggering allergic asthma, polyallergy, and...
Art v4.01 is a well-known profilin protein belonging to the pan-allergens group and is commonly involved in triggering allergic asthma, polyallergy, and cross-sensitization. It is also referred to as Wormwood due to its origin. Crude wormwood extracts are applied for allergen-specific immunotherapy (AIT). Whether the recombinant Art v4.01 (rArt v4.01) can produce in vivo immunological tolerance by subcutaneous immunotherapy (SCIT) remains elusive. In this study, to investigate the in vivo immunological response of rArt v4.01, Th2, Th1, Treg, Th17 type-related cytokines and phenotypes of immune cells were tested, facilitating the exploration of the underlying mechanisms. The expression and purification of Art v4.01 were carried out using recombinant techniques. Allergic asthma female BALB/c mice were induced by subcutaneous sensitization of wormwood pollen extract and intranasal challenges. SCIT without adjuvant was performed using the rArt v4.01 and wormwood pollen extract for 2 weeks. Following exposure to challenges, the levels of immunoglobulin E (IgE), cytokines, and inflammatory cells were assessed through enzyme-linked immunosorbent assay (ELISA) and histological examination of sera, bronchoalveolar lavage fluid (BALF), and lung tissue. These parameters were subsequently compared between treatment groups receiving rArt v4.01 and wormwood pollen extract. The rArt v4.01 protein was expressed, which had a high purity (>90%) and an allergenic potency. Compared with the pollen extract, rArt v4.01 was superior in terms of reducing the number of white blood cells (WBCs), total nucleated cells (TNCs), and monocytes (MNs) in BALF and the degree of lung inflammation (1.77±0.99 vs. 2.31±0.80, P > 0.05). Compared with the model group, only rArt v4.01 reduced serum IgE level (1.19±0.25 vs. 1.61±0.17 μg/ml, P = 0.062), as well as the levels of Th2 type-related cytokines (interleukin-4 (IL-4) (107.18±16.17 vs. 132.47±20.85 pg/ml, P < 0.05) and IL-2 (19.52±1.19 vs. 24.02±2.14 pg/ml, P < 0.05)). The study suggested that rArt v4.01 was superior to pollen extract in reducing the number of inflammatory cells in BALF, pneumonitis, levels of pro-inflammatory cytokines, and serum IgE level. These findings confirmed that Art v4.01 could be a potential candidate protein for allergen-specific immunotherapy.
Topics: Animals; Female; Asthma; Mice; Mice, Inbred BALB C; Disease Models, Animal; Immune Tolerance; Recombinant Proteins; Cytokines; Immunoglobulin E; Pollen; Desensitization, Immunologic; Allergens; Profilins; Bronchoalveolar Lavage Fluid; Injections, Subcutaneous
PubMed: 38941291
DOI: 10.1371/journal.pone.0280418 -
ELife Jun 2024Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we...
Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
Topics: SARS-CoV-2; Coronavirus Nucleocapsid Proteins; Mutation; COVID-19; Humans; Intrinsically Disordered Proteins; Phosphoproteins; Nucleocapsid Proteins; Thermodynamics; Protein Stability
PubMed: 38941236
DOI: 10.7554/eLife.94836 -
Alternative Therapies in Health and... Jun 2024Expectoration and wheezing are prevalent symptoms of respiratory diseases. Acupoint application and back tapping have shown effectiveness in alleviating cough, wheezing,...
BACKGROUND
Expectoration and wheezing are prevalent symptoms of respiratory diseases. Acupoint application and back tapping have shown effectiveness in alleviating cough, wheezing, and associated symptoms.
OBJECTIVE
This study aimed to investigate the influence of combining acupoint application with back tapping in patients experiencing expectoration and wheezing.
DESIGN
A retrospective study design was employed.
SETTING
The study was conducted at Lujiang County Hospital of Traditional Chinese Medicine.
PARTICIPANTS
A total of 96 patients presenting with expectoration and wheezing between January 2019 and June 2021 were randomly allocated into an observation group (n=48) and a control group (n=48).
INTERVENTIONS
The control group received an acupoint application using white mustard seed. In contrast, the observation group received additional back-tapping along meridians.
PRIMARY OUTCOME MEASURES
(1) Clinical efficacy; (2) traditional Chinese medicine (TCM) syndrome scores; (3) levels of inflammatory factors; (4) blood gas analysis indexes; (5) pulmonary function indexes; and (6) quality of life was assessed.
RESULTS
Following treatment, the observation group exhibited superior clinical efficacy (P < .05), reduced traditional Chinese medicine syndrome scores for cough, expectoration, and wheezing (P < .05), more pronounced improvements in inflammatory factor levels (P < .05), blood gas analysis indexes (P < .05), pulmonary function indexes (P < .05), and higher quality of life (P < .05) compared to the control group.
CONCLUSIONS
Combining acupoint application with back tapping effectively alleviated symptoms and inflammatory responses, improved blood gas and pulmonary function, and enhanced the quality of life in patients experiencing expectoration and wheezing.
PubMed: 38940795
DOI: No ID Found -
Alternative Therapies in Health and... Jun 2024To investigate the effects of holistic nursing on the quality of life overall, inflammation, and lung function in older persons experiencing acute episodes of chronic...
OBJECTIVE
To investigate the effects of holistic nursing on the quality of life overall, inflammation, and lung function in older persons experiencing acute episodes of chronic obstructive pulmonary disease (COPD).
METHODS
Considering that good nursing care improves cardiorespiratory fitness, increases treatment adherence and improves prognosis in patients with chronic obstructive pulmonary disease (COPD), From June 2019 through May 2020, 96 patients with newly diagnosed acute COPD will be recruited to take part in the trial. In total, 48 people were split into the study group and the control group at random. When compared to the control group, the research group received more comprehensive care. Procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) blood levels were compared before and after care, as were forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FEV1, and quality of life.
RESULTS
None of the demographic characteristics, including mean age, BMI, illness duration, gender, or comorbidities, differed significantly (P > .05) between the two groups. After care, serum PCT, CRP, and IL-6 levels decreased in both groups compared to pre-nursing values (P < .05); however, after care, serum PCT, CRP, and IL-6 levels were significantly lower in the study group compared to the control group. Both groups' FEV1, FVC, and FVC improved significantly (P < .05) after care compared to their baseline conditions; Statistics show that after care, the study group had significantly better FEV1, FVC, and FVC than the control group. The overall success rate of the study group was statistically significantly higher than that of the control group (P < .05). After Care, both groups' scores for illness impact, disease symptoms, and mobility restriction were much lower than they were before to care, and the difference was statistically significant (P < .05); After Care, people in the study group significantly improved on measures of mobility impairment, sickness symptoms, and disease effect compared to those in the control group. There was a statistically significant difference (P < .05) between the two groups. Patients in the study group reported significantly higher levels of satisfaction with their nursing care than patients in the control group (P < .05).
CONCLUSION
Elderly patients with acute COPD can benefit greatly from holistic nursing care in terms of reduced inflammation, enhanced lung function, and enhanced quality of life.
PubMed: 38940789
DOI: No ID Found -
Journal of Global Health Jun 2024Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that...
Analysis of clinical characteristics, prognosis and influencing factors in patients with bronchiectasis-chronic obstructive pulmonary disease overlap syndrome: A prospective study for more than five years.
BACKGROUND
Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that investigates the clinical characteristics and prognosis of bronchiectasis-COPD overlap syndrome (BCOS). Further, we aimed to explore factors associated with acute exacerbation and death in BCOS, which may be of value in its early diagnosis and intervention.
METHODS
We recruited inpatients with COPD from the second Xiangya Hospital of Central South University in China in August 2016, with follow-up until March 2022. Patients in the BCOS group had to meet the criteria for diagnosing bronchiectasis. We used self-completion questionnaires, clinical records, and self-reported data as primary data collection methods. We used Kaplan-Meier survival analyses and Cox proportional hazard models to assess the risk of severe acute exacerbation and death for BCOS during the follow-up period.
RESULTS
A total of 875 patients were included and followed up. Patients in the BCOS group had more females, fewer smokers, lower discharge COPD assessment test (CAT) scores, lower forced vital capacity (FVC), a higher likelihood of co-occurring active tuberculosis, higher levels of eosinophils and inflammatory markers, and a higher rate of positive sputum cultures for Pseudomonas aeruginosa than patients in the COPD-only group. Patients in the acute exacerbation group (AE+) were found to have lower body mass index (BMI), more frequent acute exacerbations, higher modified Medical Research Council (mMRC) dyspnoea grade on admission, higher inflammatory markers, lower FVC, higher rates of using inhaled bronchodilators, and higher rates of both positive and Pseudomonas aeruginosa positive sputum cultures. Patients in the 'death' group were older, had a lower BMI, had spent longer time in the hospital, had higher mMRC dyspnoea grade and CAT scores upon admission and discharge, had higher levels of inflammatory markers, lower rates of using inhaled bronchodilators, were more likely to have a combination of pulmonary heart disease and obsolete pulmonary tuberculosis, as well as a higher rate of fungus-positive sputum cultures. Both erythrocyte sedimentation rate at baseline and Pseudomonas aeruginosa culture positivity were confirmed as independent predictors of severe acute exacerbation in multivariate analysis during the years of follow-up. Fungus culture positivity baseline blood urea nitrogen, baseline lymphocyte count, comorbidities with obsolete pulmonary tuberculosis and comorbidities with pulmonary heart disease were verified as independent predictors of death in multivariate analysis during the years of follow-up. Kaplan-Meier curves under survival analysis demonstrated no statistically significant difference in mortality between the COPD and the BCOS groups at the full one, two, and three years of follow-up.
CONCLUSIONS
Patients with BCOS present with reduced lung function, increased susceptibility to different complications, elevated blood eosinophils and inflammatory markers, and elevated rates of positive Pseudomonas aeruginosa cultures. These distinctive markers are linked to a greater risk of severe acute exacerbations and mortality.
Topics: Humans; Female; Pulmonary Disease, Chronic Obstructive; Male; Bronchiectasis; Middle Aged; Prospective Studies; Aged; Prognosis; China; Risk Factors; Syndrome; Disease Progression
PubMed: 38940273
DOI: 10.7189/jogh.14.04129 -
Frontiers in Bioscience (Landmark... Jun 2024Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration... (Review)
Review
Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity of natural polymers and represents a strategic approach to enhance cell-scaffold interactions. The molecular interactions between MSCs and blended or functionalized scaffolds have been examined in recent studies, and it has been shown that integration can enhance MSC adhesion, proliferation, and paracrine secretion through the activation of multiple signaling pathways, such as FAK/Src, MAPK, PI3K/Akt, Wnt/β-catenin, and YAP/TAZ. Preclinical studies on small animals also reveal that the integration of electrospun scaffolds and natural polymers represents a promising approach to enhancing the delivery and efficacy of MSCs in the context of regenerating bone, cartilage, muscle, cardiac, vascular, and nervous tissues. Future research should concentrate on identifying the distinct characteristics of the MSC niche, investigating the processes involved in MSC-scaffold interactions, and applying new technologies in stem cell treatment and biofabrication to enhance scaffold design. Research on large animal models and collaboration among materials scientists, engineers, and physicians are crucial to translating these advancements into clinical use.
Topics: Humans; Mesenchymal Stem Cells; Tissue Scaffolds; Mesenchymal Stem Cell Transplantation; Animals; Polymers; Tissue Engineering
PubMed: 38940050
DOI: 10.31083/j.fbl2906228 -
Frontiers in Bioscience (Landmark... Jun 2024Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of... (Comparative Study)
Comparative Study
BACKGROUND
Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of UCMSC transplantation, such as infusion routes and doses, need to be further optimized.
METHODS
In this study, we compared the therapeutic effects of UCMSCs transplanted via intravenous injection and intratracheal instillation on lipopolysaccharide-induced ALI using a rat model. Following transplantation, levels of inflammatory factors in serum; neutrophils, total white blood cells, and lymphocytes in bronchoalveolar lavage fluid (BALF); and lung damage levels were analyzed.
RESULTS
The results indicated that UCMSCs administered via both intravenous and intratracheal routes were effective in alleviating ALI, as determined by analyses of arterial blood gas, lung histopathology, BALF contents, and levels of inflammatory factors. Comparatively, the intratracheal instillation of UCMSCs was found to result in lower levels of lymphocytes and total proteins in BALF, whereas greater reductions in the serum levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected in rats receiving intravenously injected stem cells.
CONCLUSIONS
Our findings in this study provide convincing evidence to indicate the efficacy of UCMSC therapy in the treatment of ALI mediated via different delivery routes, thereby providing a reliable theoretical basis for further clinical studies. Moreover, these findings imply that the effects obtained using the two assessed delivery routes for UCMSC transplantation are mediated via different mechanisms, which could be attributable to different cellular or molecular targets.
Topics: Animals; Acute Lung Injury; Lipopolysaccharides; Mesenchymal Stem Cell Transplantation; Umbilical Cord; Rats, Sprague-Dawley; Rats; Male; Bronchoalveolar Lavage Fluid; Mesenchymal Stem Cells; Tumor Necrosis Factor-alpha; Injections, Intravenous
PubMed: 38940047
DOI: 10.31083/j.fbl2906217 -
Admission Total Leukocyte Count as a Predictor of Mortality in Cardiac Intensive Care Unit Patients.JACC. Advances Jan 2024Inflammation is a sequela of cardiovascular critical illness and a risk factor for mortality.
BACKGROUND
Inflammation is a sequela of cardiovascular critical illness and a risk factor for mortality.
OBJECTIVES
This study aimed to evaluate the association between white blood cell count (WBC) and mortality in a broad population of patients admitted to the cardiac intensive care unit (CICU).
METHODS
This retrospective cohort study included patients admitted to the Mayo Clinic CICU between 2007 and 2018. We analyzed WBC as a continuous variable and then categorized WBC as low (<4.0 × 10/mL), normal (≥4.0 to <11.0 × 10/mL), high (≥11.0 to <22.0 × 10/mL), or very high (≥22.0 × 10/mL). The association between WBC and in-hospital mortality was evaluated using multivariable logistic regression and random forest models.
RESULTS
We included 11,699 patients with a median age of 69.3 years (37.6% females). Median WBC was 9.6 (IQR: 7.4-12.7). Mortality was higher in the low (10.5%), high (12.0%), and very high (33.3%) WBC groups relative to the normal WBC group (5.3%). A rising WBC was incrementally associated with higher in-hospital mortality after adjustment (AICc adjusted OR: 1.03 [95% CI: 1.02-1.04] per 1 × 10 increase in WBC). After adjustment, only the high (AICc adjusted OR: 1.37 [95% CI: 1.15-1.64]) and very high (AICc adjusted OR: 1.99 [1.47-2.71]) WBC groups remained associated with increased risk of in-hospital mortality.
CONCLUSIONS
Leukocytosis is associated with an increased mortality risk in a diverse cohort of CICU patients. This readily available marker of systemic inflammation may be useful for risk stratification within the increasingly complex CICU patient population.
PubMed: 38939813
DOI: 10.1016/j.jacadv.2023.100757 -
JACC. Advances Apr 2024Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada.
BACKGROUND
Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada.
OBJECTIVES
The purpose of this study was to evaluate the cost-effectiveness of using CAC score-guided statin treatment compared with universal statin therapy among intermediate-risk, primary prevention patients eligible for statins.
METHODS
A state transition, microsimulation model used data from Canadian sources and the Multi-Ethnic Study of Atherosclerosis to simulate clinical and economic consequences of cardiovascular disease from a Canadian publicly funded health care system perspective. In the CAC score-guided treatment arm, statins were started when CAC ≥1. Outcome of interest was the incremental cost-effectiveness ratio at 5 and 10 years; an incremental cost-effectiveness ratio <$50,000 per quality-adjusted life year (QALY) gained was considered cost-effective. Sensitivity analyses examined uncertainty in model parameters.
RESULTS
Compared with universal statin treatment at 5 and 10 years, CAC score-guided statin treatment was projected to increase mean costs by $326 (95% CI: $325-$326) and $172 (95% CI: $169-$175), increase mean QALYs by 0.01 (95% CI: 0.01-0.01) and 0.02 (95% CI: 0.02-0.02), and cost $54,492 (95% CI: $52,342-$56,816) and $8,118 (95% CI: $7,968-$8,279) per QALY gained, respectively. The model was most sensitive to statin cost, CAC testing cost, adherence to statin monitoring, and disutility associated with daily statin use. At 5 years, CAC score-guided statin treatment was cost-effective when CAC test costs ranged from $80 to $160 in different scenarios.
CONCLUSIONS
CAC score-guided statin initiation in comparison to universal statin treatment was borderline cost-neutral at 5 years and cost-effective at 10 years in statin-eligible Canadian patients at intermediate cardiovascular disease risk.
PubMed: 38939688
DOI: 10.1016/j.jacadv.2024.100886