Long-term associations of PM1 versus PM2.5 and PM10 with asthma and asthma-related respiratory symptoms in the middle-aged and elderly population.

Background: Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods: We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results: We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02-1.45); PM2.5: 1.24 (1.04-1.48); PM10: 1.30 (1.07-1.57)), wheeze (PM1: 1.27 (1.11-1.44); PM2.5: 1.30 (1.14-1.48); PM10: 1.34 (1.17-1.55)), persistent cough (PM1: 1.33 (1.06-1.66); PM2.5: 1.36 (1.09-1.71); PM10: 1.31 (1.02-1.68)) and dyspnoea (PM1: 2.10 (1.84-2.41); PM2.5: 2.17 (1.90-2.48); PM10: 2.29 (1.96-2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion: Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

[Study on Down-regulation of Interleukin-1ß Secretion by Inhibiting ABCC1/MRP1 Transporter].

OBJECTIVE: To screen interleukin (IL)-1ß secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice. METHODS: THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1ß was detected by ELISA, Western blot, and immunofluorescence. RESULTS: After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1ß decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1ß secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group (P < 0.05). CONCLUSION: ABCC1/MRP1 transporter is a newly discovered IL-1ß secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis: A case report.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients. There is no consensus on how to treat S. typhimurium-triggered sHLH. CASE SUMMARY: A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S. typhimurium, human rhinovirus, and Mycoplasma pneumoniae infections. At the time of admission to our institution, the patient's T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6 (IL-6), 9.1 pg/mL for IL-10, and 246.7 pg/mL for interferon-gamma (IFN-γ), for which the ratio of IL-10 to IFN-γ was 0.04. In this study, the patient received meropenem, linezolid, and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy (10 mg/kg/d for 3 d) and antishock supportive treatment twice. After careful evaluation, this patient did not receive HLH chemotherapy and recovered well. CONCLUSION: S. Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ ≤ 1.33, an IL-10 concentration ≤ 10.0 pg/mL, and/or an IFN-γ concentration ≤ 225 pg/mL at admission. Early antimicrobial and supportive treatment was sufficient, and the HLH-94/2004 protocol was not necessary under these conditions.

The predictive utility of cytokines, procalcitonin and C-reactive protein among febrile pediatric hematology and oncology patients with severe sepsis or septic shock.

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

Prognostic performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal procalcitonin.

INTRODUCTION: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT. METHODS: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia. RESULTS: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia. CONCLUSIONS: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.

The effect of the plasma methotrexate concentration during high-dose methotrexate therapy in childhood acute lymphoblastic leukemia.

Two hundred and thirty-one acute lymphoblastic leukemia (ALL) children with 1376 high-dose methotrexate (HD-MTX) courses (3-5 g/m2) were enrolled to analyze the influence of the plasma MTX concentration (CMTX) in ALL. The 24-h target peak CMTX (C24h) was set at 33 µmol/l for low-risk (LR) and 65 µmol/l for intermediate/high-risk (IR/HR) groups. The median C24h was 42.0 µmol/l and 69.7 µmol/l for LR and IR/HR groups, respectively. MTX excretion delay was observed in 14.6% of courses, which was more frequent in IR/HR groups (56.9% vs. LR group 40.2%, p = .014) and T-ALL patients (82.6% vs. B-ALL 47.1%, p = .001). MTX-related toxicities were more common in courses with MTX excretion delay. However, survival between the patients who failed to reach the target C24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, CMTX does not exert an independent influence on the prognosis of childhood ALL.

Construction of an acute myeloid leukemia prognostic model based on m6A-related efferocytosis-related genes.

Background: One of the most prevalent hematological system cancers is acute myeloid leukemia (AML). Efferocytosis-related genes (ERGs) and N6-methyladenosine (m6A) have an important significance in the progression of cancer, and the metastasis of tumors. Methods: The AML-related data were collected from The Cancer Genome Atlas (TCGA; TCGA-AML) database and Gene Expression Omnibus (GEO; GSE9476, GSE71014, and GSE13159) database. The "limma" R package and Venn diagram were adopted to identify differentially expressed ERGs (DE-ERGs). The m6A related-DE-ERGs were obtained by Spearman analysis. Subsequently, univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) were used to construct an m6A related-ERGs risk signature for AML patients. The possibility of immunotherapy for AML was explored. The pRRophetic package was adopted to calculate the IC50 of drugs for the treatment of AML. Finally, the expression of characterized genes was validated by quantitative reverse transcription-PCR (qRT-PCR). Results: Based on m6A related-DE-ERGs, a prognostic model with four characteristic genes (UCP2, DOCK1, SLC14A1, and SLC25A1) was constructed. The risk score of model was significantly associated with the immune microenvironment of AML, with four immune cell types, 14 immune checkpoints, 20 HLA family genes and, immunophenoscore (IPS) all showing differences between the high- and low-risk groups. A total of 56 drugs were predicted to differ between the two groups, of which Erlotinib, Dasatinib, BI.2536, and bortezomib have been reported to be associated with AML treatment. The qRT-PCR results showed that the expression trends of DOCK1, SLC14A1 and SLC25A1 were consistent with the bioinformatics analysis. Conclusion: In summary, 4 m6A related- ERGs were identified and the corresponding prognostic model was constructed for AML patients. This prognostic model effectively stratified the risk of AML patients.

Integrated PET/MRI With 11C-CFT and 18F-FDG for levodopa response difference in Parkinson's disease.

AIM: Parkinson's disease is one of the most common neurodegenerative diseases. Excellent levodopa responsiveness has been proposed as a characteristic supporting feature in substantiating the PD diagnosis. However, a small portion of clinically established PD patients shows poor levodopa response. This study aims to investigate brain function alterations of PD patients with poor levodopa responsiveness by PET/MRI. METHOD: A total of 46 PD patients were recruited. They all completed 11C-CFT PET/MRI scans and the acute levodopa challenge test. Among these 46 PD patients, 42 participants further underwent 18F-FDG PET/MRI scans. Clinical variables regarding demographic data, disease features and cognition scales were also collected. Based on the improvement rate of UPDRS-III, PD patients were divided into non-responders (improvement rate < 33 %) and responders (improvement rate ≥ 33 %). Statistical parametric zapping was performed to analyze molecular imaging. Dopaminergic uptake and metabolism of 70 brain regions were converted to quantitative values and expressed as standard uptake value (SUV). SUV was further normalized by the cerebellum. The resulting SUV ratios and clinical variables were then compared by SPSS. RESULTS: The difference between levodopa non-responders (n = 17) and responders (n = 29) in the UPDRS III baseline was statistically significant and the former had a lower UPDRS III baseline (19 (10, 32), p＜0.05). In contrast, no statistical difference between these two groups was found in age, gender, disease duration, cognition, motor subtype and Hoehn-Yahr stage. Dopaminergic uptake differences between levodopa non-responders (n = 17) and responders (n = 29) were shown in the left inferior frontal cortex (1.00 ± 0.09 vs 1.07 ± 0.08, p < 0.05 and FDR < 0.2), the right posterior cingulum (1.10 ± 0.10 vs 1.20 ± 0.13, p < 0.05 and FDR < 0.2) and the right insula (1.21 ± 0.12 vs 1.30 ± 0.10, p < 0.05 and FDR < 0.2). The metabolic alterations between levodopa non-responders (n = 16) and responders (n = 26) were shown in the right supplementary motor area (1.30 (1.18, 1.39) vs 1.41 (1.31, 1.53), p < 0.05 and FDR < 0.2), right precuneus (1.37 ± 0.10 vs 1.47 ± 0.18, p < 0.05 and FDR < 0.2), right parietal cortex (1.14 ± 0.15 vs 1.27 ± 0.21, p < 0.05 and FDR < 0.2), right supramarginal gyrus (1.16 (1.12, 1.26) vs 1.25 (1.14, 1.46), p < 0.05 and FDR < 0.2), right postcentral gyrus (1.15 (1.08, 1.32) vs 1.24 (1.17, 1.39), p < 0.05 and FDR < 0.2), medulla (0.75 ± 0.07 vs 0.80 ± 0.07, p < 0.05 and FDR < 0.2), right rolandic operculum (1.25 (1.18, 1.32) vs 1.33 (1.25, 1.50), p < 0.05 and FDR < 0.2), right olfactory (0.95 (0.91, 1.01) vs 1.01 (0.95, 1.15), p < 0.05 and FDR < 0.2), the right insula (1.15 (1.06, 1.22) vs 1.21 (1.12, 1.35), p < 0.05 and FDR < 0.2) and the left cerebellum crus (0.96 (0.91, 1.01) vs 0.92 (0.86, 0.96), p < 0.05 and FDR < 0.2). CONCLUSIONS: PD patients with poor response to levodopa showed less severe impairment of baseline motor symptoms, more severe dopaminergic deficits in the left inferior frontal, right posterior cingulate cortex and the right insula, and lower metabolism in the right supplementary motor area, right precuneus, right parietal cortex, right supramarginal gyrus, right postcentral gyrus, medulla, right rolandic operculum, right olfactory, the right insula and higher metabolism in the left cerebellum crus.

[Research Progress in Diagnostic Reference Levels in Interventional Radiology].

During interventional procedures,subjects are exposed to direct and scattered X-rays.Establishing diagnostic reference levels is an ideal way to optimize the radiation dose and reduce radiation hazard.In recent years,diagnostic reference levels in interventional radiology have been established in different countries.However,because of the too many indicators for characterizing the radiation dose,the indicators used to establish diagnostic reference levels vary in different countries.The research achievements in this field remain to be reviewed.We carried out a retrospective analysis of the definition,establishment method,application,and main factors influencing the dose difference of the diagnostic reference level,aiming to provide a basis for establishing the diagnostic reference level for interventional procedures in China.

[Noise Exposure and Stress Hormone Levels:A Review].

Noise is one of the most common environmental hazards to which people are exposed,and the exposure to noise can cause not only hearing but also non-hearing damage.Although noise under safety limits may not affect the auditory system,it can cause changes in stress hormone levels,which is harmful to health.However,the current studies about the impact of noise on health mainly focus on the auditory system,and little is known about the relationship between noise and stress hormone levels.Therefore,this paper reviews the studies involving noise exposure and stress hormone levels,aiming to provide ideas for strengthening the prevention and control of noise hazards.

Ruxolitinib Treatment of Steroid-Refractory Graft-versus-Host Disease in Children: A Case Series and Review of the Literature.

BACKGROUND: Ruxolitinib has been increasingly used in the treatment of steroid-refractory graft-versus-host disease (SR-GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. However, there are limited data on the use of ruxolitinib in children. OBJECTIVE: This study aimed to assess the efficacy and toxicity of ruxolitinib in the treatment of SR-GVHD in children. PATIENTS AND METHODS: Data of patients who suffered from SR-GVHD after allo-HSCT and received ruxolitinib treatment between June 2018 and December 2020 at our center were analyzed retrospectively. The characteristics of patients, the dosage of ruxolitinib, the response, toxicity, and the survival data were collected. RESULTS: A total of 14 pediatric patients were diagnosed with SR-GVHD after allo-HSCT and received ruxolitinib. The age of the patients ranged from 3 months to 12 years old. The dosage of ruxolitinib ranged from 2.5 mg twice daily to 7.5 mg twice daily, mainly according to patient weight. The total overall response rate (ORR) was 64.3% (9/14), with 63.6% (7/11) in aGVHD and 67% (2/3) in cGVHD. Of the 14 patients, adverse effects were observed in 9 patients (64.3%), including cytopenia, infection, and elevated alanine aminotransferase. In addition, seven reports on the treatment of SR-GVHD in children with ruxolitinib were included for systematic analysis, with the ORR ranging from 45 to 87% in aGVHD and 70-91% in cGVHD. CONCLUSION: Given its effectiveness and safety, ruxolitinib could be used to treat SR-GVHD in children after HSCT.

Elastin-Derived VGVAPG Fragment Decorated Cell-Penetrating Peptide with Improved Gene Delivery Efficacy.

Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and mßCD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.

Low-dose decitabine for refractory thrombocytopenia following allogeneic hematopoietic stem cell transplantation in children: A pilot study.

Refractory thrombocytopenia is a critical complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is not sensitive to conventional treatment and often leads to lower overall survival and disease-free survival. Previous studies have showed the efficacy and safety of low-dose decitabine for adults' refractory prolonged isolated thrombocytopenia in hematologic malignancy after allo-HSCT. However, clinical data on pediatric patients or non-hematologic malignancies are lacking. Herein, we evaluated the safety and efficacy of low-dose decitabine in nine children with persistent thrombocytopenia after HSCT. Patients received decitabine at 3.5 mg/m2, 5 mg/m2 or 10 mg/m2 respectively for three to five consecutive days according to underlying diseases and hyperplastic state of bone marrow. Six patients reached sustained platelets count more than 100 × 109/L, two patients achieved platelet transfusion independence. The total response rate was 88.8 % (8/9). One patient died from severe infection because of persistent agranulocytosis longer than 3 weeks. In conclusion, the present study supports the safety and efficacy of low-dose decitabine for treatment of refractory thrombocytopenia after allogeneic HSCT in children.

Establishment of a risk model correlated with metabolism based on RNA-binding proteins associated with cell pyroptosis in acute myeloid leukemia.

Background: RNA-binding protein (RBP) regulates acute myeloid leukemia (AML) by participating in mRNA editing and modification. Pyroptosis also plays an immunomodulatory function in AML. Therefore, this study aimed to identify pyroptosis-related RBP genes that could predict the prognosis of AML patients. Methods: AML related expression data were downloaded from the UCSC website and Gene Expression Omnibus (GEO) database. Pyroptosis-RPB-related differentially expressed genes (PRBP-DEGs) were conducted with a protein-protein interactions (PPI) network to screen out the key PRBP-DEGs, based on which a risk model was constructed by Cox analysis, and evaluated by plotting Receiver operating characteristic (ROC) curves and survival curves. Independent prognostic analysis was performed and a nomogram was constructed. Finally, enrichment analysis was performed for high and low risk groups. Reuslts: A total of 71 PRBP-DEGs were obtained and a pyroptosis-RPB-related risk model was constructed based on IFIT5, MRPL14, MRPL21, MRPL39, MVP, and PUSL1 acquired from Cox analysis. RiskScore, age, and cytogenetics risk category were identified as independent prognostic factors, and the nomogram based on these independent prognostic factors could accurately predict 1-, 3- and 5-year survival of AML patients. Gene set enrichment analysis (GSEA) showed that the high-risk and low-risk groups were mainly enriched in metabolic- and immune-related processes and pathways. Conclusion: In this study, a risk score model correlated with metabolism based on RNA-binding proteins associated with cell pyroptosis in acute myeloid leukemia was established, which provided a theoretical basis and reference value for therapeutic studies and prognosis of AML.

Cross-sectional study on prevalence and risk factors for falls among the elderly in communities of Guangdong province, China.

OBJECTIVE: This study aims to investigate the prevalence and risk factors of falls among the elderly in Guangdong, China. METHODS: A cross-sectional study was conducted in six communities of Guangdong province. People over 60 years old were selected with multistage random-cluster sampling. Data on falls within the previous 12 months and fall-related risk factors were collected through a face-to-face interview. RESULTS: The prevalence of falls among older adults was 11.9% (95% CI: 11.0% to 12.8%) among 5374 interviewees. The common injuries caused by falls were bruises/scrapes (40.0%) and fractures (15.5%), and most people fall while doing housework (35.0%). Univariate analysis showed that 14 factors were associated with falls among older adults, including gender, age, residence, occupation, education level, balance ability, situation of cognition, disease, depression, living arrangement, marital status, the behaviour of exercise, drinking and drug use (p<0.05). Multivariate analysis showed that the associated factors of falls among older adults included woman (OR=1.68, 95% CI: 1.40 to 2.02), age from 70 to 79 years (OR=1.31, 95% CI: 1.09 to 1.58), age over 80 (OR=1.63, 95% CI: 1.25 to 2.13), impaired balance ability (OR=1.45, 95% CI: 1.20 to 1.75), exercise several times per month (OR=1.69, 95% CI: 1.13 to 2.53), polypharmacy (OR=1.54, 95% CI: 1.19 to 2.00), cognition impairment (OR=1.35, 95% CI: 1.08 to 1.69), mild depression (OR=1.89, 95% CI: 1.47 to 2.45) and moderate depression (OR=3.07, 95% CI: 1.99 to 4.73). CONCLUSIONS: The hazards caused by falls to the elderly in China cannot be ignored. A multidimensional customised fall prevention programme should be considered to reduce the risk of falls among the elderly based on the results above.

Metagenomic next-generation sequencing for the diagnosis of fever of unknown origin in pediatric patients with hematological malignancy.

BACKGROUND AND AIMS: The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in identifying microbiological etiologies in pediatric patients with hematological malignancies undergoing fever of unknown origin (FUO). METHODS: A total of 147 children with hematological malignancy suffering febrile diseases without definite microbiological etiologies under conventional tests were enrolled. The clinical record, serum inflammatory biomarkers and mNGS results were analyzed. RESULTS: At least one microorganism was identified by mNGS in 112 of 147 patients (76.2 %). Two or more types of organisms were detected simultaneously in 35.7 % (40/112) of samples. Of the 112 cases with positive mNGS results, the reported microorganisms were considered as etiologies of fever in 50 (44.6 %) cases. The initial antimicrobial regimens were adjusted according to the mNGS results in 48 cases, with 41 patients' febrile diseases resolved. Totally, 27.9 % (41/147) of patients benefit from mNGS. High IL-6 (>390 pg/mL) level was associated with bacterial infection and could help to interpret the results of mNGS. CONCLUSION: mNGS is a novel approach to determine the microbiological etiology of FUO in hematological malignancy patients, which benefits about a quarter of all patients tested. Integration of IL-6 can improve the diagnostic precision of bacterial infection.

Different patterns of exosomal α-synuclein between Parkinson's disease and probable rapid eye movement sleep behavior disorder.

BACKGROUND AND PURPOSE: The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. METHODS: In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. RESULTS: It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p < 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p < 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes. CONCLUSIONS: Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.