Objective To investigate the effects of synovial fluid from patients with rheumatoid arthritis(RA)on the polarization of normal neutrophils and the MEK/ERK signaling pathway,thereby providing experimental evidence to elucidate the pathological mechanisms of RA and offering novel insights into its treatment.Methods Synovial fluid samples were collected from 20 RA patients and 20 osteoarthritis(OA)patients.ELISA was used to measure the levels of interferon-gamma(IFN-γ),tumor necrosis factor-alpha(TNF-α),transforming growth factor-beta(TGF-β)and interleukin-8(IL-8)in the synovial fluid.Neutrophils were isolated from the peripheral blood of healthy donors,and their purity was confirmed by flow cytometry.Neutrophils were then treated with synovial fluid and divided into four groups:Control(untreated),RA(treated with 10％RA synovial fluid),OA(treated with 10％OA synovial fluid),and anti-IFN-β(treated with 20 μg anti-IFN-β antibody as an N2-type control).Western blot was used to assess the changes in the expression of IFN-γ,TNF-α,TGF-β,MEK,p-MEK,ERK and p-ERK.Additionally,the MEK inhibitor PD0325901 was used to block the MEK/ERK pathway,and subsequent changes in IFN-γ and TGF-β expression in neutrophils were evaluated.Results The levels of IFN-γ,TNF-α,TGF-β and IL-8 in the synovial fluid of RA patients were significantly higher than those in OA patients.After intervention with RA synovial fluid,the relative expression of IFN-γ and TNF-α in neutrophils were significantly increased compared to those in the untreated control group and the OA group.While,TGF-β expression in the RA group was lower than that in both the control and anti-IFN-β groups.The relative expression of p-MEK and p-ERK in the RA group were significantly higher than those in the control,OA and Anti-IFN-β groups.Upon addition of the MEK inhibitor,the relative expression of p-MEK and p-ERK were reduced.Furthermore,in both the RA and OA groups,the relative expression levels of IFN-γ decreased,while the expression of TGF-β increased.Conclusion Synovial fluid from RA patients contains higher of IFN-γ,TNF-αand TGF-β,which activate neutrophils through phosphorylation of the MEK/ERK signaling pathway,promoting their polarization toward the pro-inflammatory N1 phenotype.

Objective To systematically retrieve,evaluate and summarize the related evidences of plate-let implantation delayed management in the patients with allogeneic hematopoietic stem cell transplantation.Methods According to the"6S"model,the clinical decision systems,guidelines network,professional associa-tion websites and databases were retrieved to collect the evidences regarding the platelet implantation delayed management in the patients with allogeneic hematopoietic stem cell transplantation,the retrieval time limit was from the database establishment to May 2024.Two researchers independently conducted the quality eval-uation of the literatures,evidence extraction and evidence integration.Results A total of 17 articles were fi-nally included,including 1 guideline,2 clinical decisions,3 systematic reviews,5 expert consensus and 6 ran-domized controlled trials.A total of 24 pieces of evidences were summarized in 5 aspects,including the pre-transplantation evaluation and prevention,application of mesenchymal stem cells,thrombopoietic drugs man-agement,blood transfusion support and complication management such as bleeding.Conclusion The medical and care staffs should carry out the best evidence practice for platelet implantation delayed management in the patients with allogeneic hematopoietic stem cell transplantation by combining with the domestic clinical situa-tion to reduce the hemorrhage in multiple organ systems after transplantation and improve the survival quality.

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.

Objective To investigate the effects of synovial fluid from patients with rheumatoid arthritis(RA)on the polarization of normal neutrophils and the MEK/ERK signaling pathway,thereby providing experimental evidence to elucidate the pathological mechanisms of RA and offering novel insights into its treatment.Methods Synovial fluid samples were collected from 20 RA patients and 20 osteoarthritis(OA)patients.ELISA was used to measure the levels of interferon-gamma(IFN-γ),tumor necrosis factor-alpha(TNF-α),transforming growth factor-beta(TGF-β)and interleukin-8(IL-8)in the synovial fluid.Neutrophils were isolated from the peripheral blood of healthy donors,and their purity was confirmed by flow cytometry.Neutrophils were then treated with synovial fluid and divided into four groups:Control(untreated),RA(treated with 10％RA synovial fluid),OA(treated with 10％OA synovial fluid),and anti-IFN-β(treated with 20 μg anti-IFN-β antibody as an N2-type control).Western blot was used to assess the changes in the expression of IFN-γ,TNF-α,TGF-β,MEK,p-MEK,ERK and p-ERK.Additionally,the MEK inhibitor PD0325901 was used to block the MEK/ERK pathway,and subsequent changes in IFN-γ and TGF-β expression in neutrophils were evaluated.Results The levels of IFN-γ,TNF-α,TGF-β and IL-8 in the synovial fluid of RA patients were significantly higher than those in OA patients.After intervention with RA synovial fluid,the relative expression of IFN-γ and TNF-α in neutrophils were significantly increased compared to those in the untreated control group and the OA group.While,TGF-β expression in the RA group was lower than that in both the control and anti-IFN-β groups.The relative expression of p-MEK and p-ERK in the RA group were significantly higher than those in the control,OA and Anti-IFN-β groups.Upon addition of the MEK inhibitor,the relative expression of p-MEK and p-ERK were reduced.Furthermore,in both the RA and OA groups,the relative expression levels of IFN-γ decreased,while the expression of TGF-β increased.Conclusion Synovial fluid from RA patients contains higher of IFN-γ,TNF-αand TGF-β,which activate neutrophils through phosphorylation of the MEK/ERK signaling pathway,promoting their polarization toward the pro-inflammatory N1 phenotype.

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.

Objective To construct and apply a management plan for microaspiration of oropharyngeal secretions in ICU intubated patients.Methods Based on evidence summaries and expert consultation,a management plan for microaspiration of oropharyngeal secretions in ICU intubated patients was constructed,consisting of 19 items covering 7 aspects including identification of risk factors,position management,tube and cuff selection,cuff management,mechanical ventilation management,pain and sedation management,removal of oropharyngeal and subglottic secretions,and oral care.Convenience sampling was used to select 141 ICU intubated patients from a tertiary A comprehensive hospital in Suzhou from June,2022 to September,2023.Patients were divided into an experimental group(n=72)and a control group(n=69)according to the wards.The experimental group received the management plan for microaspiration of oropharyngeal secretions in ICU intubated patients.The control group received the nursing bundle for ventilator associated pneumonia(VAP).The incidence and time from intubation to microaspiration and VAP,duration of mechanical ventilation,ICU length of stay,and disease outcome were compared between the 2 groups.Results The incidence of microaspiration of oropharyngeal secretions,the duration of mechanical ventilation,time from intubation to microaspiration showed significant differences between the 2 groups(P<0.05).There were no significant differences in the incidence of ventilator associated pneumonia,ICU length of stay,and disease outcome between the 2 groups(P>0.05).The time from intubation to VAP in the experimental group was 7.5 days,and that in the control group was 3.8 days.Conclusion The application of the management plan for microaspiration of orophaiyngeal secretions in ICU intubated patients is beneficial for reducing the incidence of microaspiration,delaying the time from intubation to microaspiration and VAP,and shortening the duration of mechanical ventilation.

Objective:To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) on the discharge outcome in elderly patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis (IVT).Methods:Elderly patients with AIS received IVT in the Department of Neurology, the Second Affiliated Hospital of Soochow University from August 2018 to August 2020 were retrospectively included. The modified Rankin Scale was used to evaluate discharge outcome, and the score >2 was defined as poor outcome. Symptomatic intracranial hemorrhage (sICH) was defined as any intracranial hemorrhage found on imaging examination accompanied by neurological deterioration, where the National Institutes of Health Stroke Scale (NIHSS) score increased by ≥4 from baseline or bleeding led to death. Multivariate logistic regression analysis was used to determine independent risk factors for sICH and poor discharge outcome. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of NLR for sICH and poor discharge outcome. Results:A total of 228 elderly patients with AIS receiving IVT were enrolled, including 118 males (51.8%), aged 73.64±8.16 years, with a baseline NIHSS score of 6.23±6.54. Ninety patients (39.5%) had poor outcome at discharge, and 16 (7.0%) developed sICH. Univariate analysis showed that the NLR in the poor outcome group was significantly higher than that in the good outcome group ( P<0.01). Multivariate logistic regression analysis showed that a higher NLR was an independent risk factor for poor discharge outcome (odds ratio [ OR] 1.245, 95% confidence interval [ CI] 1.044-1.484; P< 0.05) and sICH ( OR 1.124, 95% CI 1.010-1.251; P<0.05). ROC curve analysis showed that the area under the curve of NLR for predicting poor discharge outcome was 0.693 (95% CI 0.620-0.765; P<0.01). The optimal cutoff value was 4.345. Its corresponding sensitivity and specificity were 47.8% and 87.7%, respectively. The area under the curve of NLR for predicting sICH was 0.651 (95% CI 0.498-0.804; P<0.05). The optimal cutoff value was 3.515. Its corresponding sensitivity and specificity were 68.8% and 61.8%, respectively. Conclusions:A higher NLR is independently associated with sICH and poor discharge outcome in elderly patients with AIS receiving IVT, and have certain predictive value for sICH and poor discharge outcome.

Objective:To investigate the effect of high glucose on the release of interleukin (IL)-1β and IL-18 in placental trophoblast by activating NLRP3 inflammasome.Methods:Gestational diabetes mellitus(GDM) placentas and control placentas were collected and the expression levels of NLRP3 and Caspase-1 were determined. Human placental trophoblast HTR-8/SVneo were cultured and divided into control group(5.5 mmol/L glucose), high glucose group(25 mmol/L glucose), DMSO+ high glucose group, and Ac-YVAD-cmk(NLRP3 inflammasome inhibitor)+ high glucose group. The expression levels of NLRP3 and Caspase-1 in cells as well as the contents of IL-1β and IL-18 in the medium were determined.Results:The expression levels of NLRP3 and Caspase-1 in GDM placenta were higher than those in control placenta( P<0.05) and positively correlated with homeostasis model assessment of insulin resistant index(HOMA-IR) and fasting insulin. The expression levels of NLRP3 and Caspase-1 in HTR-8/SVneo cells and the secretion levels of IL-1β and IL-18 in high glucose group were higher than those in control group( P<0.05). Ac-YVAD-cmk significantly suppressed high glucose-stimulated IL-1β and IL-18 secretion( P<0.05). Conclusion:High glucose promotes the release of IL-1β and IL-18 from placental trophoblast via activating NLRP3 inflammasome.

Objective:To explore the abnormal features of cortical thickness of brain regions in patients with alcohol dependence (PADs) after acute detoxication and the correlation with clinical features of PADs.Methods:In this study, male inpatients with alcohol dependence (patient group, n=33) and healthy controls (control group, n=35) matched with age and education were enrolled during the period of Apr 2017 to Apr 2018. Brain functional magnetic resonance imaging (MRI) data, general demographic and clinical information were collected. FreeSurfer software was used to process the MRI data and compute the bilateral cortical thickness across 74 brain regions. Analysis of covariance (ANCOVA) was performed to analyse the differences of cortical thickness in different brain regions between the two groups, and the correlation between the cortex thickness and their clinical features in PADs was explored by using correlation analysis. Results:Compared with HCs, PADs showed significantly decreased cortical thickness of brain regions in the left middle and pole occipital, right superior occipital gyri, bilateral superior and inferior parietal gyri, and right intraparietal sulcus (all P<0.000 34, after Bonferroni correction). Positive correlation was found between the thickness of left superior parietal gyrus (SPG) and initial drinking age ( r=0.428, P=0.024) in PADs. Conclusion:The cortex thickness reduction of bilateral posterior parietal cortex might be a more characteristic injury in PADs. Furthermore, the initial drinking age may have a more obvious effect on the cortex of the left SPG.

Coronavirus disease 2019 has attracted worldwide attention. Different populations have different levels of risk perception in the face of public health emergencies, and risk perception is related to reported preventive health behaviors. This article reviews relevant theories and assessment tools of risk perception of public health emergencies and influencing factors of risk perception of public health emergencies among different populations, in order to provide theoretical basis for the formulation of relevant measures and provide reference for improving the prevention and control behavior of individuals.