INTRODUCTION: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically. METHODS: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups. RESULTS: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups ( P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life. CONCLUSIONS RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients.
Humans ; Arthritis, Rheumatoid/diagnosis* ; Male ; Female ; Middle Aged ; Rheumatoid Factor/blood* ; Anti-Citrullinated Protein Antibodies/blood* ; Adult ; Quality of Life ; Prospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Peptides, Cyclic/immunology* ; Prednisolone/therapeutic use* ; Surveys and Questionnaires ; Severity of Illness Index ; Prognosis

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.

Objective: To analyze the epidemiological characteristics and related factors of hepatitis C in Beijing City from 2004 to 2021. Methods: Descriptive epidemiological method and Joinpoint regression were used to analyze the trend and other epidemiological characteristics of hepatitis C in Beijing City from 2004 to 2021 in National Notifiable Disease Reporting System. According to a 1∶1 matched case-control study design, logistic regression was used to investigate the risk factors of hepatitis C infection in 2021. Results: From 2004 to 2021, the reported incidence of hepatitis C in Beijing City ranged from 2.37/100 000 to 10.46/100 000. The reported cases were mainly aged 30-60 years, and most of them were chronic. The reported incidence of hepatitis C showed an initial increase from 2004 to 2006 (APC=45.37%, 95%CI:-1.56%-114.69%), and declined after 2006 (APC=-9.21%, 95%CI:-10.70%-7.70%). Logistic analysis showed that history of surgery (OR=1.84, 95%CI: 1.08-3.14) and previous blood transfusion (OR=34.22, 95%CI: 8.05-145.41) were risk factors for hepatitis C infection. Conclusion: The reported incidence of hepatitis C in Beijing City increases first and decreases later. It currently remains at a low level. The risk factors of infection are surgery and blood transfusion history. Safe blood supply and preventing iatrogenic transmission should be focused on the prevention of hepatitis C transmission.
Humans ; Beijing/epidemiology* ; Case-Control Studies ; Hepatitis C/prevention & control* ; Risk Factors ; Incidence

Objective: To analyze the epidemiological characteristics and related factors of hepatitis C in Beijing City from 2004 to 2021. Methods: Descriptive epidemiological method and Joinpoint regression were used to analyze the trend and other epidemiological characteristics of hepatitis C in Beijing City from 2004 to 2021 in National Notifiable Disease Reporting System. According to a 1∶1 matched case-control study design, logistic regression was used to investigate the risk factors of hepatitis C infection in 2021. Results: From 2004 to 2021, the reported incidence of hepatitis C in Beijing City ranged from 2.37/100 000 to 10.46/100 000. The reported cases were mainly aged 30-60 years, and most of them were chronic. The reported incidence of hepatitis C showed an initial increase from 2004 to 2006 (APC=45.37%, 95%CI:-1.56%-114.69%), and declined after 2006 (APC=-9.21%, 95%CI:-10.70%-7.70%). Logistic analysis showed that history of surgery (OR=1.84, 95%CI: 1.08-3.14) and previous blood transfusion (OR=34.22, 95%CI: 8.05-145.41) were risk factors for hepatitis C infection. Conclusion: The reported incidence of hepatitis C in Beijing City increases first and decreases later. It currently remains at a low level. The risk factors of infection are surgery and blood transfusion history. Safe blood supply and preventing iatrogenic transmission should be focused on the prevention of hepatitis C transmission.
Humans ; Beijing/epidemiology* ; Case-Control Studies ; Hepatitis C/prevention & control* ; Risk Factors ; Incidence

ObjectiveTo explore the variation rules and health risks of trihalomethane in regional drinking water， and to provide evidence for the innovative water processing technology and the optimization of drinking water quality. MethodsBased on regional drinking water sanitation monitoring， non-parametric rank sum test was used to analyze the effects of residual trihalomethane production in different periods and with disinfection methods. The United States environmental protection agency （USEPA） classic "four-step" health risk assessment model was used to evaluate the carcinogenic risk and non-carcinogenic risk of trihalomethane through drinking water exposure. ResultsThe yield of trichloromethane in wet season was 6.3 μg·L^-1， which was higher than that in dry season. Compared with chlorination pretreatment， ozone pretreatment reduced the content of bromomethane dichloromethane. Compared to liquid chlorine disinfection， sodium hypochlorite treatment incresed the levels of trichloromethane and bromomethane chloride. Although the total carcinogenic and non-carcinogenic risks of trihalomethane in drinking water in the region were at safe levels， they were above the acceptable limits occasionally. The highest carcinogenic risk of trihalomethane were dichlorobromomethane and chlorodibromomethane，and the highest non-carcinogenic risk was trichloromethane. The health risk of children was 1.2 times higher than that for adults. ConclusionThe production of residual trihalomethane in drinking water in this area is relatively low， which is less harmful to the health of adults and children. Monitoring， including other disinfection byproducts， should continue and appropriate disinfection techniques for drinking water should be explored.

Objective:To explore the multi-component， multi-target and multi-pathway mechanism of Astragali Radix against immunoglobulin A nephropathy （IgAN） by network pharmacology， aiming to provide evidence for its basic research and clinical application. Method:The active chemical components and targets of Astragali Radix and targets associated with IgAN were obtained by literature mining and GeneCards， Traditinal Chinese Medicine Integrated Database （TCMID）， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. Cytoscape 3.7.1 software was used to draw network interaction diagrams. The key targets of Astragali Radix against IgAN were searched by network topology. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis involved in the targets were analyzed by different packages in R programming language. On this basis， cell experiments in vitro were carried out to verify the activation effect of astragaloside Ⅳ on phosphatidylinositol 3-kinase/protein kinase B/tumor suppressor gene protein 53 （PI3K/Akt/p53） signaling pathway of human mesangial cells. Result:A total of 25 active components and 49 ingredient-disease targets of Astragali Radix were screened. The GO enrichment analysis included 84 items， which were related to nuclear hormone receptor binding， nuclear receptor activity， deoxyribonucleic acid binding transcriptional activation activity and other aspects. The KEGG pathway enrichment analysis included 88 KEGG pathways， which were closely related to PI3K/Akt signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， advanced glycation end product/receptor of advanced glycation end product （AGE/RAGE） signaling pathway and others. Cell experiments in vitro confirmed that astragaloside Ⅳ could effectively inhibit the platelet derived growth factor-BB （PDGF-BB）-induced proliferation of human mesangial cells by regulating PI3K/Akt/p53 signaling pathway. Conclusion:The active ingredients of Astragali Radix may play a role in the treatment of IgAN by acting on targets and pathways related to apoptosis， oxidative stress， inflammation response and others， providing ideas and directions for the new drug development and mechanism study of IgAN.

The human UDP-glucuronosyltransferase 1A1 (UGT1A1), one of the most essential conjugative enzymes, is responsible for the metabolism and detoxification of bilirubin and other endogenous substances, as well as many different xenobiotic compounds. Deciphering UGT1A1 relevance to human diseases and characterizing the effects of small molecules on the activities of UGT1A1 requires reliable tools for probing the function of this key enzyme in complex biological matrices. Herein, an easy-to-use assay for highly-selective and sensitive monitoring of UGT1A1 activities in various biological matrices, using liquid chromatography with fluorescence detection (LC-FD), has been developed and validated. The newly developed LC-FD based assay has been confirmed in terms of sensitivity, specificity, precision, quanti-tative linear range and stability. One of its main advantages is lowering the limits of detection and quantification by about 100-fold in comparison to the previous assay that used the same probe substrate, enabling reliable quantification of lower amounts of active enzyme than any other method. The precision test demonstrated that both intra- and inter-day variations for this assay were less than 5.5％. Further-more, the newly developed assay has also been successfully used to screen and characterize the regu-latory effects of small molecules on the expression level of UGT1A1 in living cells. Overall, an easy-to-use LC-FD based assay has been developed for ultra-sensitive UGT1A1 activities measurements in various biological systems, providing an inexpensive and practical approach for exploring the role of UGT1A1 in human diseases, interactions with xenobiotics, and characterization modulatory effects of small mole-cules on this conjugative enzyme.

To evaluate the correlation between the radiomics signature of hepatobiliary phase imaging of gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid(Gd-EOB-DTPA)enhanced magnetic resonance imaging(MRI)and Child-Pugh of liver cirrhosis,establish nomogram prediction model,and assess the predictive value of quantitative assessment of liver reserve function of patients with liver cirrhosis. One hundred patients with liver cirrhosis who met the inclusion criteria were divided into 52 patients with Child-Pugh grade A and 48 patients with Child-Pugh grade B+C according to Child-Pugh classification criteria,and were randomly divided into training set and test set at a proportion of 7∶3.The AK software was used to extract the imaging features of the Gd-EOB-DTPA-enhanced MRI hepatobiliary images of the patients in the training set,and the least absolute shrinkage and selection operator feature selection algorithm was used to reduce the dimension of the data,select the features,and construct the radiomics tags.According to the radiomics label Rad-score,a line chart(nomogram)prediction model was established to predict the Child-Pugh B+C level of liver reserve function.The model was applied to the training set and test set respectively,and the diagnostic efficiency was quantitatively evaluated by receiver operating characteristic(ROC)curve. After dimension reduction and screening of 396 texture feature parameters extracted by AK software,7 image feature parameters were obtained.According to the above characteristics,the radiomics tag Rad-score was constructed and the nomogram prediction model was created.The differences of Rad-score scores between Child-Pugh A and Child-Pugh B+C groups in training set and test set were statistically analyzed by Wilcoxon rank sum test(=0.000, =0.001).The diagnostic efficacy of nomogram prediction model for predicting Child-Pugh B+C grade of liver reserve function in the ROC curve of training set and test set was 0.88 and 0.86 respectively. The nomogram prediction model created according to the radiomics tag Rad-score of patients with liver cirrhosis with different liver reserve functions can be used as a more accurate and reliable auxiliary detection tool for liver reserve function.It provides a new means for clinicians to evaluate liver reserve function more accurately.
Contrast Media ; Gadolinium DTPA ; Humans ; Liver Cirrhosis ; Magnetic Resonance Imaging