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Scientific Reports Jul 2024In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable...
In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable interest. Cytokine research, especially Th-17 cytokine research on GAD patients, is limited. Here, we aim to assess the role of interleukin-17A (IL-17A) and interleukin-23A (IL-23A) in the pathophysiology and development of GAD. This investigation included 50 GAD patients and 38 age-sex-matched healthy controls (HCs). A psychiatrist diagnosed patients with GAD and assessed symptom severity using the DSM-5 and the GAD-7 scales. The serum concentrations of IL-17A and IL-23A were determined using commercially available ELISA kits. GAD patients exhibited elevated levels of IL-17A (77.14 ± 58.30 pg/ml) and IL-23A (644.90 ± 296.70 pg/ml) compared to HCs (43.50 ± 25.54 pg/ml and 334.40 ± 176.0 pg/ml). We observed a positive correlation between disease severity and cytokine changes (IL-23A: r = 0.359, p = 0.039; IL-17A: r = 0.397, p = 0.032). These findings indicate that IL-17A and IL-23A may be associated with the pathophysiology of GAD. ROC analysis revealed moderately higher AUC values (IL-23A: 0.824 and IL-17A: 0.710), demonstrating their potential to discriminate between patients and HCs. Also, the sensitivity values of both cytokines were relatively higher (IL-23A: 80.49% and IL-17A: 77.27%). According to the present findings, there may be an association between peripheral serum levels of IL-17A and IL-23A and the pathophysiology and development of GAD. These altered serum IL-17A and IL-23A levels may play a role in directing the early risk of developing GAD. We recommend further research to ascertain their exact role in the pathophysiology and their performance as risk assessment markers of GAD.
Topics: Humans; Interleukin-17; Male; Female; Anxiety Disorders; Adult; Interleukin-23 Subunit p19; Case-Control Studies; Biomarkers; Middle Aged; Severity of Illness Index
PubMed: 38956309
DOI: 10.1038/s41598-024-66131-9 -
Communications Medicine Jul 2024Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand...
BACKGROUND
Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand binding. Its expression on immune cells in human tumors is poorly understood.
METHODS
An antibody that distinguishes human CEACAM1 from other highly related CEACAM family members was labeled with Tb and inserted into a panel of antibodies that included specificity for programmed cell death protein 1 (PD1) and PD-L1, which are targets of immunotherapy, to gain a data-driven immune cell atlas using cytometry by time-of-flight (CyTOF). A detailed inventory of CEACAM1, PD1, and PD-L1 expression on immune cells in metastatic lesions to lymph node or soft tissues and peripheral blood samples from patients with treatment-naive and -resistant melanoma as well as peripheral blood samples from healthy controls was performed.
RESULTS
CEACAM1 is absent or at low levels on healthy circulating immune cells but is increased on immune cells in peripheral blood and tumors of melanoma patients. The majority of circulating PD1-positive NK cells, innate T cells, B cells, monocytic cells, dendritic cells, and CD4 T cells in the peripheral circulation of treatment-resistant disease co-express CEACAM1 and are demonstrable as discrete populations. CEACAM1 is present on distinct types of cells that are unique to the tumor microenvironment and exhibit expression levels that are highest in treatment resistance; this includes tumor-infiltrating CD8 T cells.
CONCLUSIONS
To the best of our knowledge, this work represents the first comprehensive atlas of CEACAM1 expression on immune cells in a human tumor and reveals an important correlation with treatment-resistant disease. These studies suggest that agents targeting CEACAM1 may represent appropriate partners for PD1-related pathway therapies.
PubMed: 38956268
DOI: 10.1038/s43856-024-00525-8 -
Signal Transduction and Targeted Therapy Jul 2024More than 90% of hepatocellular carcinoma (HCC) cases develop in the presence of fibrosis or cirrhosis, making the tumor microenvironment (TME) of HCC distinctive due to...
More than 90% of hepatocellular carcinoma (HCC) cases develop in the presence of fibrosis or cirrhosis, making the tumor microenvironment (TME) of HCC distinctive due to the intricate interplay between cancer-associated fibroblasts (CAFs) and cancer stem cells (CSCs), which collectively regulate HCC progression. However, the mechanisms through which CSCs orchestrate the dynamics of the tumor stroma during HCC development remain elusive. Our study unveils a significant upregulation of Sema3C in fibrotic liver, HCC tissues, peripheral blood of HCC patients, as well as sorafenib-resistant tissues and cells, with its overexpression correlating with the acquisition of stemness properties in HCC. We further identify NRP1 and ITGB1 as pivotal functional receptors of Sema3C, activating downstream AKT/Gli1/c-Myc signaling pathways to bolster HCC self-renewal and tumor initiation. Additionally, HCC cells-derived Sema3C facilitated extracellular matrix (ECM) contraction and collagen deposition in vivo, while also promoting the proliferation and activation of hepatic stellate cells (HSCs). Mechanistically, Sema3C interacted with NRP1 and ITGB1 in HSCs, activating downstream NF-kB signaling, thereby stimulating the release of IL-6 and upregulating HMGCR expression, consequently enhancing cholesterol synthesis in HSCs. Furthermore, CAF-secreted TGF-β1 activates AP1 signaling to augment Sema3C expression in HCC cells, establishing a positive feedback loop that accelerates HCC progression. Notably, blockade of Sema3C effectively inhibits tumor growth and sensitizes HCC cells to sorafenib in vivo. In sum, our findings spotlight Sema3C as a novel biomarker facilitating the crosstalk between CSCs and stroma during hepatocarcinogenesis, thereby offering a promising avenue for enhancing treatment efficacy and overcoming drug resistance in HCC.
Topics: Liver Neoplasms; Humans; Carcinoma, Hepatocellular; Tumor Microenvironment; Semaphorins; Integrin beta1; Mice; Signal Transduction; Hepatic Stellate Cells; Neuropilin-1; Cell Line, Tumor; Neoplastic Stem Cells; Animals; Gene Expression Regulation, Neoplastic; Sorafenib; Cancer-Associated Fibroblasts; Disease Progression
PubMed: 38956074
DOI: 10.1038/s41392-024-01887-0 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jul 2024The prevalence of pulmonary aspergillosis is increasing in patients with chronic obstructive pulmonary disease (COPD) and can manifest in different forms such as...
The prevalence of pulmonary aspergillosis is increasing in patients with chronic obstructive pulmonary disease (COPD) and can manifest in different forms such as invasive pulmonary aspergillosis (IPA), chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). With the variations of individual conditions such as immune status, these forms of the disease may transform into each other or even overlap. Moreover, the atypical clinical manifestations and the limited use of invasive sampling techniques have posed a challenge to the diagnosis and treatment of invasive pulmonary aspergillosis in patients with COPD. To provide recommendations for the management of pulmonary aspergillosis in patients with COPD and to construct a clinical workflow, the consensus panel reviewed the evidence and critically appraised the existing studies. As the majority of the recommendations were supported by low levels of evidence, the evidence levels were not listed in the consensus and the strong and weak recommendations were expressed as "recommend" and "suggest", respectively.Recommendations for COPD with IPA: The Panel recommends that high-resolution chest computed tomography (HRCT) be performed in patients suspected with IPA. If IPA cannot be excluded by CT scanning, mycological examination of sputum and bronchoalveolar lavage fluid (BALF) is recommended. Bronchoscopy and BALF -related examination are recommended in COPD patients with respiratory symptoms such as dyspnea despite the use of broad-spectrum antibiotics and systemic glucocorticoids and pulmonary infiltrates observed on chest CT. If the diagnosis is in doubt in patients with probable IPA, histopathological examination is recommended. In COPD patients with an acute infection of more than 10 days' duration, the Panel recommended the detection of -specific IgG antibodies in peripheral blood to aid in the diagnosis of IPA, especially in those who cannot obtain BALF. It is not recommended to initiate antifungal therapy based on clinical symptoms such as cough, fever, and dyspnea empirically in COPD patients. In critically ill patients (such as those admitted to ICU and those with respiratory failure) who are unresponsive to broad-spectrum antibiotic treatment and have imaging findings consistent with IPA, patients with HRCT or bronchoscopy findings consistent with airway invasive aspergillosis, patients with a history of oral or intravenous glucocorticoid use in the past 3 months, or patients with a history of airway infection or colonization, empirical antifungal therapy may be initiated after a comprehensive evaluation of infection risk, and at the same time, pathogen examination should be started as early as possible. Voriconazole, isavuconazole, and posaconazole are recommended as the first-line treatments for COPD with IPA. Echinocandins and amphotericin B may be used as alternative options. Antifungal treatment for COPD with IPA should be continued for at least 6-12 weeks. The duration of antifungal therapy should be determined based on clinical symptoms, pulmonary imaging, and microbiological test results. Significant lesion absorption and stabilization, as well as the elimination of related risk factors, are important references for discontinuation of treatment.Recommendations on COPD with CPA: Chest CT scan and dynamic observation are recommended for COPD with suspected CPA. Peripheral blood -specific IgG antibody testing is recommended in COPD patients with suspected CPA. For those who are difficult to diagnose by routine methods or need further differential diagnosis, pulmonary tissue histopathological examination is recommended. Oral itraconazole solution or voriconazole tablets are recommended as the first-line treatment options for COPD with CPA. Oral isavuconazole capsules or enteric-coated posaconazole tablets can be used as an alternative. Intravenous administration of echinocandins or amphotericin B (deoxycholate or lipid formulations) are suggested as a second-line treatment options in cases of triazole treatment failure, resistance, or intolerance. Antifungal treatment for COPD with CPA should be continued for at least 6 months, and for patients with CCPA for at least 9 months. In those with cavities communicating with the bronchial lumen, if systemic antifungal therapy is ineffective or cannot be tolerated due to adverse reactions, and surgery is also not feasible, the Panel suggests considering nebulized inhalation of amphotericin B and intracavitary injection of amphotericin B or azoles (voriconazole, itraconazole) to control recurrent hemoptysis.Recommendations on COPD with sensitization: When COPD patients present with refractory wheezing and/or rapid decline in lung function, it is recommended that an assessment for sensitization be performed, including -specific IgE, skin antigen test, -specific IgG, total IgE, blood eosinophil count, and sputum examination. The Panel recommends that antifungal therapy should not be routinely initiated in COPD patients with sensitization. For those who meet the diagnostic criteria for ABPA, antifungal therapy is suggested. The most commonly used medication is oral itraconazole solution, but other azoles such as voriconazole, isavuconazole and posaconazole enteric-coated tablets can also be chosen. The general course of antifungal therapy is 3-6 months.Recommendations on the use of glucocorticoids in COPD with pulmonary aspergillosis: In exacerbating COPD patients with secondary IPA or subacute invasive aspergillosis, the Panel suggests that the use of glucocorticoids should be controlled. For COPD patients with concomitant CPA who experience exacerbations with predominantly wheezing, it is suggested that short-term, low-dose glucocorticoids be considered on the basis of antifungal treatment to control symptoms. Glucocorticoid use for COPD exacerbations is suggested to be guided by peripheral blood eosinophil count. It is recommended to avoid systemic glucocorticoids and long-term or high-dose inhaled glucocorticoids (ICS) in stable COPD patients with concomitant CPA. In patients with concomitant sensitization and persistent wheezing despite standardized COPD treatment or patients with ABPA, the Panel recommends systemic glucocorticoids in combination with antifungal therapy and consideration of the use of ICS to reduce the dose of systemic glucocorticoids. Close monitoring for progression to IPA or subacute invasive aspergillosis is essential during treatment.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Aspergillosis; Consensus
PubMed: 38955746
DOI: 10.3760/cma.j.cn112147-20231228-00399 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024This study aims to explore the diagnostic value of inflammation-related genes in peripheral blood mononuclear cells in bronchopulmonary dysplasia (BPD). By using...
This study aims to explore the diagnostic value of inflammation-related genes in peripheral blood mononuclear cells in bronchopulmonary dysplasia (BPD). By using bioinformatics analysis, three datasets including GSE32472, GSE125873, and GSE220135, which contain whole-genome expression profile data of 251 neonates, were included. The GSE32472 dataset was used as a training dataset to detect differentially expressed genes between non-BPD and BPD neonates in peripheral blood mononuclear cells. The gene enrichment analysis (GSEA) was used to detect the pathway enrichment of up-regulated genes in BPD newborns. The main regulatory factors analysis (MRA) algorithm was used to filter the main regulatory genes in the inflammation-related pathway (GO:0006954). After obtaining the main regulatory genes, the expression of the main regulatory genes in the GSE32472, GSE125873, and GSE220135 datasets was detected. Through the logistic regression model, risk scoring was conducted for neonates, and the risk scores of non-BPD and BPD neonates were compared. Lastly, the classification performance of the model was evaluated using the area under the curve (AUC). The results showed that compared with non-BPD neonates, there were 486 up-regulated genes and 433 down-regulated genes in the peripheral blood mononuclear cells of BPD neonates. The inflammation-related pathway was highly enriched in the up-regulated genes. Ultimately, phospholipase C beta 1 (PLCB1), nidogen 1 (NID1), serum response factor binding protein 1 (SRFBP1), centrosomal protein 72 (CEP72), excision repair cross complementation group 6 like (ERCC6L), and peptidylprolyl isomerase like 1 (PPIL1) were identified as the main regulatory genes. The prediction model's calculation formula for risk score was PLCB1×0.26+NID1×0.97+SRFBP1×1.58+CEP72×(-0.36)+ERCC6L×2.14+PPIL1×0.67. The AUCs in the GSE32472 test dataset, GSE125873 dataset, and GSE220135 dataset were 0.88, 0.86, and 0.89, respectively. This prediction model could distinguish between non-BPD and BPD neonates. In conclusion, the prediction model based on inflammation-related pathway genes has a certain diagnostic value for BPD.
Topics: Humans; Bronchopulmonary Dysplasia; Infant, Newborn; Inflammation; Leukocytes, Mononuclear; Gene Expression Profiling; Computational Biology
PubMed: 38955739
DOI: 10.3760/cma.j.cn112150-20231012-00257 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes...
To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, =490), complication group 1 (1 microvascular complications, =217), and complication group 2 (2 or more microvascular complications, =129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant (=537.470, 791.690, 136.340, <0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) μg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) μg/ml] and complication group 2 [30.42 (12.53, 47.26) μg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant (=210.020, <0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients (=-0.431, -0.372, -0.546, <0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes (=2.261, 95%: 1.564-3.269), increased HbA1c (=2.040, 95%: 1.456-2.858), and increased HOMA-IR (=2.158, 95%: 1.484-3.137) and decreased 1, 5-AG (=2.512, 95%: 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients (<0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95%: 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95%: 0.692-0.767). Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.
Topics: Humans; Diabetes Mellitus, Type 2; Insulin Resistance; Cross-Sectional Studies; Retrospective Studies; Deoxyglucose; Blood Glucose; Male; Female; Insulin; Middle Aged; Diabetic Angiopathies
PubMed: 38955736
DOI: 10.3760/cma.j.cn112150-20240219-00129 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in...
To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China. The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function. The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the (, ) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95%)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all >0.05). Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.
Topics: Humans; Cadmium; Middle Aged; China; Aged; Male; Leukocyte Count; Female; Adult; Aged, 80 and over; Creatinine
PubMed: 38955731
DOI: 10.3760/cma.j.cn112150-20240222-00137 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and...
To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance. Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups. A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant (=1.541 for local adverse reactions in the control group, =0.718 for the observation group; =0.483 for systemic adverse reactions in the control group, =0.179 for the observation group, value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups (=4.147, <0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status (-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all -values <0.001, and -values of the observation group were 15.480, 27.087, 28.938, all -values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment (-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all -values <0.001, and -values of 9.436, 13.184, and 22.377 in the observation group, respectively; all -values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years (-values 0.621, 0.473, 1.825, and 0.342, respectively, and -values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points (-values of 1.663, 0.095, 0.305, 0.951, -values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment (-values of the conventional group were 3.453, 5.469, 6.273, -values <0.05, and the -values of the observation group were 2.900, 4.575, 5.988, -values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing (-value in the conventional group was -5.328, -4.254, -0.690, -value was 0.000, 0.000, 0.492, respectively, and -value in the observation group was -6.087, -5.087, -0.324, -value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years (-values of 0.723, 1.553, 0.766, and 0.234, respectively; -values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE (-values of 0.170, -0.166, -0.449, 0.839, -values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 (-values 1.507, 1.467, -0.337, 0.804, -values 0.134, 0.145, 0.737, 0.422, respectively). Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.
Topics: Humans; Child; Desensitization, Immunologic; Retrospective Studies; Child, Preschool; Adolescent; Animals; Immunoglobulin E; Asthma; Allergens; Male; Rhinitis, Allergic; Female; Mites; Treatment Outcome
PubMed: 38955723
DOI: 10.3760/cma.j.cn112150-20230915-00194 -
Medicina Clinica Jul 2024There is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting....
BACKGROUND AND AIMS
There is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in "real life" in Spain.
METHODS
A prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy.
RESULTS
We included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents.
CONCLUSIONS
Despite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the "real world" remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic.
PubMed: 38955604
DOI: 10.1016/j.medcli.2024.04.020 -
FEBS Letters Jul 2024The poliovirus (PV) enters the central nervous system (CNS) via the bloodstream, suggesting the existence of a mechanism to cross the blood-brain barrier. Here, we...
The poliovirus (PV) enters the central nervous system (CNS) via the bloodstream, suggesting the existence of a mechanism to cross the blood-brain barrier. Here, we report that PV capsid proteins (VP1 and VP3) can penetrate cells, with VP3 being more invasive. Two independent parts of VP3 are responsible for this function. Both peptides can penetrate human umbilical cord vascular endothelial cells, and one peptide of VP3 could also penetrate peripheral blood mononuclear cells. In an in vitro blood-brain barrier model using rat-derived astrocytes, pericytes, and endothelial cells, both peptides were observed to traverse from the blood side to the brain side at 6 h after administration. These results provide insights into the molecular mechanisms underlying PV invasion into the CNS.
PubMed: 38955545
DOI: 10.1002/1873-3468.14974