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Biomolecules May 2024Acute pancreatitis (AP) is a complex inflammatory condition that can lead to systemic inflammatory responses and multiple organ dysfunction. This study investigates the...
Acute pancreatitis (AP) is a complex inflammatory condition that can lead to systemic inflammatory responses and multiple organ dysfunction. This study investigates the role of Galectin-3 (Gal-3), a β-galactoside-binding lectin, in modulating acquired immune responses in AP. Acute pancreatitis was induced by ligation of the bile-pancreatic duct in wild-type and Galectin-3-deficient C57BL/6 mice. We determined the phenotypic and molecular features of inflammatory cells, serum concentrations of amylase, pancreatic trypsin activity, and pancreatic and lung pathology. Galectin-3 deficiency decreased the total number of CD3CD49 T cells and CD4 T helper cells, downregulated the production of inflammatory cytokine and IFN-γ, and increased the accumulation of IL-10-producing Foxp3 T regulatory cells and regulatory CD4 T cells in the pancreata of diseased animals. The deletion of Galectin-3 ameliorates acute pancreatitis characterized by lowering serum amylase concentration and pancreatic trypsin activity, and attenuating of the histopathology of the lung. These findings shed light on the role of Galectin-3 in acquired immune response in acute pancreatitis and identify Galectin-3 as an attractive target for investigation of the immunopathogenesis of disease and for consideration as a potential therapeutic target for patients with acute inflammatory disease of the pancreas.
Topics: Animals; Pancreatitis; Galectin 3; Mice; T-Lymphocytes, Regulatory; Mice, Inbred C57BL; Mice, Knockout; Acute Disease; Male; Amylases
PubMed: 38927046
DOI: 10.3390/biom14060642 -
Journal of Cardiothoracic Surgery Jun 2024As the pediatric patient with right pulmonary artery agenesis (PAA) matured, she progressively presented symptoms of pulmonary hypertension and hemoptysis. There is... (Review)
Review
Embolization treatment of right pulmonary artery agenisis with patent ductus arteriosus causing pulmonary hypertension and hemoptysis: a case report and literature review.
As the pediatric patient with right pulmonary artery agenesis (PAA) matured, she progressively presented symptoms of pulmonary hypertension and hemoptysis. There is limited clinical literature on this condition, and currently, there is no consensus regarding its diagnosis and treatment. This article presents a case study of a 16-year-old female patient with right pulmonary artery hypoplasia, providing a comprehensive summary and analysis of her developmental progression, pathology, diagnosis, and treatment.
Topics: Humans; Female; Hemoptysis; Pulmonary Artery; Adolescent; Embolization, Therapeutic; Hypertension, Pulmonary; Ductus Arteriosus, Patent
PubMed: 38926785
DOI: 10.1186/s13019-024-02883-9 -
Journal of Cardiothoracic Surgery Jun 2024At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is... (Comparative Study)
Comparative Study
BACKGROUND
At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is insufficient. This report aimed to compare the outcomes of three-port and four-port da Vinci robot-assisted thoracoscopic surgery for radical dissection of lung cancer.
METHODS
171 consecutive patients who presented to our hospital from January 2020 to October 2021 with non-small cell lung cancer and treated with da Vinci robot-assisted thoracoscopic surgery for radical resection of lung cancer were retrospectively collected and divided into the three-port group (n = 97) and the four-port group (n = 74). The general clinical data, perioperative data and life quality were individually compared between the two groups.
RESULTS
All the 171 patients successfully underwent surgeries. Compared to the four-port group, the three-port group had comparable baseline characteristics in terms of age, sex, tumor location, tumor size, history of chronic disease, pathological type, and pathological staging. The three-port group also had shorter operation time, less intraoperative blood loss, lower chest tube drainage volume, shorter postoperative hospitalization stay durations, but showed no statistically significant difference (P > 0.05). Postoperative 24, 48 and 72 h visual analogue scale pain scores were lower in the three-port group (p < 0.001). No significant difference was observed between the two groups in the hospitalization costs (P = 0.664), number or stations of total lymph node dissected (p > 0.05) and postoperative respiratory complications (P > 0.05).
CONCLUSIONS
The three-port robot-assisted thoracoscopic surgery is safe and effective and took better outcomes than the four-port robot-assisted thoracoscopic surgery in non-small cell lung cancer.
Topics: Humans; Robotic Surgical Procedures; Male; Female; Lung Neoplasms; Retrospective Studies; Middle Aged; Aged; Carcinoma, Non-Small-Cell Lung; Thoracic Surgery, Video-Assisted; Pneumonectomy; Operative Time; Treatment Outcome
PubMed: 38926727
DOI: 10.1186/s13019-024-02920-7 -
BMC Pulmonary Medicine Jun 2024This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission.
BACKGROUND
This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission.
METHODS
This study retrospectively extracted data from MIMIC-IV database, ultimately including 3776 AECOPD patients. The patients were randomly divided into a training set (n = 2643) and a validation set (n = 1133) in a 7:3 ratio. First, LASSO regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Subsequently, a multifactorial Cox regression analysis was employed to establish a predictive model. Thirdly, the model was validated using ROC curves, Harrell's C-index, calibration plots, DCA, and K-M curve.
RESULT
Eight predictive indicators were selected, including blood urea nitrogen, prothrombin time, white blood cell count, heart rate, the presence of comorbid interstitial lung disease, heart failure, and the use of antibiotics and bronchodilators. The model constructed with these 8 predictors demonstrated good predictive capabilities, with ROC curve areas under the curve (AUC) of 0.858 (0.836-0.881), 0.773 (0.746-0.799), 0.736 (0.701-0.771) within 3, 7, and 14 days in the training set, respectively and the C-index was 0.743 (0.723-0.763). Additionally, calibration plots indicated strong consistency between predicted and observed values. DCA analysis demonstrated favorable clinical utility. The K-M curve indicated the model's good reliability, revealed a significantly higher RF occurrence probability in the high-risk group than that in the low-risk group (P < 0.0001).
CONCLUSION
The nomogram can provide valuable guidance for clinical practitioners to early predict the probability of RF occurrence in AECOPD patients, take relevant measures, prevent RF, and improve patient outcomes.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Intensive Care Units; Middle Aged; Databases, Factual; ROC Curve; Risk Assessment; Aged, 80 and over; Nomograms; Risk Factors; Pulmonary Disease, Chronic Obstructive
PubMed: 38926685
DOI: 10.1186/s12890-024-03099-2 -
Scientific Reports Jun 2024Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to...
Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to distinguish patients with lung cancer from healthy individuals. Additionally, we sought to develop a deep learning model incorporating cfDNA methylation and fragment size profiles. To achieve this, we utilized methylation data collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Then we generated methylated DNA immunoprecipitation sequencing and genome-wide Enzymatic Methyl-seq (EM-seq) form lung cancer tissue and plasma. Using these data, we selected 366 methylation markers. A targeted EM-seq panel was designed using the selected markers, and 142 lung cancer and 56 healthy samples were produced with the panel. Additionally, cfDNA samples from healthy individuals and lung cancer patients were diluted to evaluate sensitivity. Its lung cancer detection performance reached an accuracy of 81.5% and an area under the receiver operating characteristic curve of 0.87. In the serial dilution experiment, we achieved tumor fraction detection of 1% at 98% specificity and 0.1% at 80% specificity. In conclusion, we successfully developed and validated a combination of methylation panel and a deep learning model that can distinguish between patients with lung cancer and healthy individuals.
Topics: Humans; Lung Neoplasms; DNA Methylation; Deep Learning; Biomarkers, Tumor; Female; Male; Middle Aged; Aged; Cell-Free Nucleic Acids; ROC Curve
PubMed: 38926407
DOI: 10.1038/s41598-024-63411-2 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma.
METHODS
In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (=49) and an SCIT group (=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT.
RESULTS
Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events.
CONCLUSIONS
SCIT is an effective and safe treatment for allergic asthma in children.
Topics: Humans; Asthma; Male; Child; Female; Animals; Prospective Studies; Injections, Subcutaneous; Pyroglyphidae; Child, Preschool; Desensitization, Immunologic; Adolescent
PubMed: 38926371
DOI: 10.7499/j.issn.1008-8830.2309137 -
Nature Communications Jun 2024Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and...
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/- drug treatment; +/- cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies.
Topics: Induced Pluripotent Stem Cells; Humans; Myocytes, Cardiac; Myocardial Contraction; Software; Cell Differentiation; Single-Cell Analysis; Cells, Cultured
PubMed: 38926342
DOI: 10.1038/s41467-024-49755-3 -
Journal For Immunotherapy of Cancer Jun 2024Lung metastasis is the primary cause of breast cancer-related mortality. Neutrophil extracellular traps (NETs) are involved in the progression of breast cancer. However,...
BACKGROUND
Lung metastasis is the primary cause of breast cancer-related mortality. Neutrophil extracellular traps (NETs) are involved in the progression of breast cancer. However, the mechanism of NET formation is not fully understood. This study posits that tumor cell-released autophagosomes (TRAPs) play a crucial role in this process.
METHODS
TRAPs were isolated from breast cancer cell lines to analyze their impact on NET formation in both human and mouse neutrophils. The study used both in vitro and in vivo models, including Toll-like receptor 4 (TLR4/) mice and engineered breast cancer cell lines. Immunofluorescence, ELISA, Western blotting, RNA sequencing, and flow cytometry were employed to dissect the signaling pathways leading to NET production and to explore their immunosuppressive effects, particularly focusing on the impact of NETs on T-cell function. The therapeutic potential of targeting TRAP-induced NETs and their immunosuppressive functions was evaluated using DNase I and αPD-L1 antibodies. Clinical relevance was assessed by correlating circulating levels of TRAPs and NETs with lung metastasis in patients with breast cancer.
RESULTS
This study showed that TRAPs induced the formation of NETs in both human and mouse neutrophils by using the high mobility group box 1 and activating the TLR4-Myd88-ERK/p38 signaling axis. More importantly, PD-L1 carried by TRAP-induced NETs inhibited T-cell function in vitro and in vivo, thereby contributing to the formation of lung premetastatic niche (PMN) immunosuppression. In contrast, KD-4T1 breast tumors with decreased circulating TRAPs in vivo reduced the formation of NETs, which in turn attenuated the immunosuppressive effects in PMN and resulted in a reduction of breast cancer pulmonary metastasis in murine models. Moreover, treatment with αPD-L1 in combination with DNase I that degraded NETs restored T-cell function and significantly reduced tumor metastasis. TRAP levels in the peripheral blood positively correlated with NET levels and lung metastasis in patients with breast cancer.
CONCLUSIONS
Our results demonstrate a novel role of TRAPs in the formation of PD-L1-decorated NETs, which may provide a new strategy for early detection and treatment of pulmonary metastasis in patients with breast cancer.
Topics: Animals; Humans; Mice; Female; Breast Neoplasms; Lung Neoplasms; Extracellular Traps; B7-H1 Antigen; Autophagosomes; T-Lymphocytes; Cell Line, Tumor
PubMed: 38926151
DOI: 10.1136/jitc-2024-009082 -
The Journal of Maternal-fetal &... Dec 2024Preeclampsia is associated with adverse perinatal outcomes, including fetal growth restriction (FGR) and preterm delivery. The maternal serum ratio of soluble fms-like... (Observational Study)
Observational Study
INTRODUCTION
Preeclampsia is associated with adverse perinatal outcomes, including fetal growth restriction (FGR) and preterm delivery. The maternal serum ratio of soluble fms-like tyrosine kinase receptor-1 (sFlt-1) to placental growth factor (PlGF) can be used to evaluate placental dysfunction in cases of preeclampsia and FGR. A need for delivery within 2 days has been recommended for sFlt-1/PlGF ratios > 655 (normal ratio < 38) measured before 34 weeks' gestation. However, few studies have assessed this recommendation in a real-world setting and there remains a need for further evidence-based guidance on the use of the ratio in delivery timing planning in this situation.
AIM
To assess the need for delivery within 2 days associated with sFlt-1/PlGF ratios > 655 before 34 weeks' gestation.
METHODS
A retrospective audit of all sFlt-1/PlGF ratio test results obtained at a single maternity hospital between September 2016 and November 2022. The primary outcome was time to delivery after recording a ratio > 655 in patients with a pregnancy between 20 + 0 and 33 + 6 weeks' gestation. Statistical analysis was performed using IBM SPSS Statistics v29.0.0.0.
RESULTS
During the study period a total of 33 patients with suspected or confirmed preeclampsia and/or FGR recorded sFlt-1/PlGF ratios > 655 before 34 + 0 weeks' gestation. Amongst cases with ratios > 655, median time to delivery was 4 days (IQR 1.0-9.0), with 14 (42.4%) delivering in ≤ 2 days, 8 (24.2%) delivering between 2 and 7 days and 11 (33.3%) delivering after 7 days. A significant inverse correlation was observed between time to delivery and gestational age at the time of ratio testing ( = -0.484, = 0.004).
DISCUSSION
This study provides updated recommendations on the use of the sFlt-1/PlGF ratio in predicting the risk of imminent delivery amongst those with high ratios > 655 measured before 34 weeks' gestation. Our results suggest that the risk of imminent delivery can be stratified based on ratio level and gestational age, which in combination with the results of other clinical assessments, can be used to plan delivery timing and allow for considerations of fetal lung maturing corticosteroid and neuroprotective magnesium sulfate therapies prior to delivery.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Vascular Endothelial Growth Factor Receptor-1; Placenta Growth Factor; Adult; Premature Birth; Pre-Eclampsia; Gestational Age; Biomarkers; Fetal Growth Retardation; Infant, Newborn
PubMed: 38926094
DOI: 10.1080/14767058.2024.2371047 -
BMJ (Clinical Research Ed.) Jun 2024To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19.
OBJECTIVE
To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19.
DESIGN
Population based study.
SETTING
UK.
PARTICIPANTS
1 650 052 individuals registered with a general practice contributing to Clinical Practice Research Datalink and newly diagnosed with at least one CVD from 1 January 2000 to 30 June 2019.
MAIN OUTCOME MEASURES
The primary outcome was incident diagnosis of CVD, comprising acute coronary syndrome, aortic aneurysm, aortic stenosis, atrial fibrillation or flutter, chronic ischaemic heart disease, heart failure, peripheral artery disease, second or third degree heart block, stroke (ischaemic, haemorrhagic, and unspecified), and venous thromboembolism (deep vein thrombosis or pulmonary embolism). Disease incidence rates were calculated individually and as a composite outcome of all 10 CVDs combined and were standardised for age and sex using the 2013 European standard population. Negative binomial regression models investigated temporal trends and variation by age, sex, and socioeconomic status.
RESULTS
The mean age of the population was 70.5 years and 47.6% (n=784 904) were women. The age and sex standardised incidence of all 10 prespecified CVDs declined by 19% during 2000-19 (incidence rate ratio 2017-19 2000-02: 0.80, 95% confidence interval 0.73 to 0.88). The incidence of coronary heart disease and stroke decreased by about 30% (incidence rate ratios for acute coronary syndrome, chronic ischaemic heart disease, and stroke were 0.70 (0.69 to 0.70), 0.67 (0.66 to 0.67), and 0.75 (0.67 to 0.83), respectively). In parallel, an increasing number of diagnoses of cardiac arrhythmias, valve disease, and thromboembolic diseases were observed. As a result, the overall incidence of CVDs across the 10 conditions remained relatively stable from the mid-2000s. Age stratified analyses further showed that the observed decline in coronary heart disease incidence was largely restricted to age groups older than 60 years, with little or no improvement in younger age groups. Trends were generally similar between men and women. A socioeconomic gradient was observed for almost every CVD investigated. The gradient did not decrease over time and was most noticeable for peripheral artery disease (incidence rate ratio most deprived least deprived: 1.98 (1.87 to 2.09)), acute coronary syndrome (1.55 (1.54 to 1.57)), and heart failure (1.50 (1.41 to 1.59)).
CONCLUSIONS
Despite substantial improvements in the prevention of atherosclerotic diseases in the UK, the overall burden of CVDs remained high during 2000-19. For CVDs to decrease further, future prevention strategies might need to consider a broader spectrum of conditions, including arrhythmias, valve diseases, and thromboembolism, and examine the specific needs of younger age groups and socioeconomically deprived populations.
Topics: Humans; Female; Male; United Kingdom; Incidence; Aged; Middle Aged; Cardiovascular Diseases; Adult; Aged, 80 and over; Social Class; Age Distribution; Sex Distribution; Young Adult
PubMed: 38925788
DOI: 10.1136/bmj-2023-078523