OBJECTIVE:Interstitial lung disease (ILD) is a frequent complication in both anti-synthetase syndrome (ASyS) and primary Sjögren's disease (pSjD), but the clinical and molecular phenotype of patients with overlapping ASyS and pSjD (ASyS-SjD) remains poorly defined. This study aimed to characterize the clinical, serological, radiological and transcriptomic features of ASyS-SjD patients with ILD, and to determine whether this overlap represents a distinct disease entity. METHODS:We retrospectively analysed 131 ASyS, 78 pSjD and 42 ASyS-SjD patients from the First Affiliated Hospital of Nanjing Medical University between June 2020 and June 2023. Clinical features, laboratory findings, pulmonary function and HRCT patterns were compared. RNA sequencing was performed on peripheral blood mononuclear cells from eight ASyS, nine pSjD, 10 ASyS-SjD patients and 10 controls. RESULTS:ASyS-SjD patients had earlier ILD onset (10.0 vs 67.5 months, P < 0.001), more RP-ILD (16.7% vs 3.9%, P = 0.015) and worse pulmonary function than pSjD patients (FEV1%: 63.5% vs 76.6%, P = 0.010; FVC%: 64.2% vs 77.0%, P = 0.024; DLCO%: 60.7% vs 72.6%, P = 0.046). HRCT showed predominantly NSIP in ASyS-SjD (75.6%), similar to ASyS, with rare LIP (2.4%). ILD characteristics between ASyS-SjD and ASyS were comparable. Transcriptomics revealed shared inflammation with ASyS plus unique profibrotic signalling in ASyS-SjD. CONCLUSION:ASyS-SjD exhibits an ASyS-like clinical phenotype with additional profibrotic features, suggesting it may represent an overlap subtype rather than a coincidental coexistence. While ILD in ASyS-SjD appears more aggressive than in SjD, it is not clearly more severe than in ASyS.

Rapidly progressive interstitial lung disease (RP-ILD) is a severe, often fatal complication in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5+ DM). Early prediction of RP-ILD still remains challenging. We aimed to explore the link between anti-MDA5 IgG subtypes and ILD prognosis in individuals with MDA5+ DM. In a retrospective study involving 71 MDA5+ DM-ILD patients, initial serum titers of anti-MDA5 IgG subtypes were measured using indirect immunofluorescence. We then analyzed the associations between these IgG subclasses and the development of RP-ILD. Of the 71 patients, 30

Abstract Background Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5+DM patients. Methods Serums were collected from 39 patients with anti-MDA5+DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay. Results Serum BAFF level was higher in anti-MDA5+DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5+DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5+DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609—54.769; p = 0.013). Conclusions Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5+DM patients.

OBJECTIVE:To summarize the clinical characteristics of 57 patients diagnosed with anti-glycyl tRNA synthetase (anti-EJ) positive antisynthetase syndrome (ASS), a subtype of anti-glycyl tRNA positive ASS, complicated by interstitial lung disease (ILD), and to investigate the factors asso-ciated with ILD recurrence. METHODS:A retrospective analysis was conducted on the clinical data of 57 anti-EJ positive ASS patientswho were treated at the First Affiliated Hospital of Nanjing Medical University from January 1, 2020 to June 30, 2024. The data collected included demographic information, clinical characteristics, laboratory test results, chest CT findings, and pulmonary function tests. The characteristics of ILD recurrence were also analyzed. RESULTS:All the 57 patients with anti-EJ positive ASS were diagnosed with ILD. The mean age at disease onset was (58.18±10.27) years, with a mean disease duration of 3.00 (2.00, 16.00) months. Among the patients, 70. 18% were female, 87.72% experienced a cough, 70. 18% had expectoration, 89.47% reported respiratory difficulties, and 14.04% developed respiratory failure. The results of pulmonary function test showed that the percentage of forced vital capacity (FVC) in the normal predicted value (FVC%), the percentage of forced expiratory volume in the first second (FEV1) in the normal predicted value (FEV1%) and the percentage of diffusion lung carbon monoxide (DLCO) in the normal predicted value (DLCO%) were 59.36±21.41, 58.34±19.46 and 58.17±27.95, respectively. The oxygenation index was (363.24±99.42) mmHg. Chest CT imaging showed that nonspecific interstitial pneumonia (NSIP) was the most common radiographic pattern. Among the 46 patients who completed a follow-up of more than 12 months, 21 cases (45.65%) showed recurrence of ILD. The average age of onset for the recurrence group was (61.38±8.63) years, while that for the non-recurrence group was (55.28±11.85) years, with a difference approaching statistical significance (P=0.056). Further analysis showed that the ESR (erythrocyte sedimentation rate) level was significantly higher in the recurrence group than in the non-recurrence group [(50.48±29.64) mm/h vs. 30.28±23.97) mm/h, P=0.025], and the IgM (immune globulin M) level was also significantly higher in the recurrence group (P=0.042). Moreover, the CD8+T proportion was significantly higher in the recurrence group than in the non-recurrence group (25.48±11.81 vs. 18.59± 8.53, P=0.027). Despite the fact that the recurrence group had a higher baseline age, higher ESR, IgM, and CD8+T proportion, multivariate binary logistic regression analysis showed that these indicators were not independent risk factors for ILD recurrence. CONCLUSION:ILD is the most common clinical manifestation in patients with anti-EJ positive ASS, with a significant impact on pulmonary function. Although the patients responded well to a combination of glucocorticoid and immunosuppressive therapies, the recurrence rate remains high, particularly in those with increased sputum production, and elevated ESR. Close monitoring and early intervention for high-risk patients are essential to improving long-term outcomes.

BackgroundMost studies have explored the relationship between serum total folate and nonalcoholic fatty liver disease (NAFLD) in adults, but there has been no study on the relationship between different folate forms and hepatic steatosis or liver stiffness in adolescents.ObjectiveTo investigate the association of different folate forms with hepatic steatosis or liver stiffness in adolescents, and further explore the intermediary role of BMI in this relationship.MethodsThe cross-sectional study included 549 participants from the 2017-2018 National Health and Nutrition Inspection Survey (NHANES) survey cycle who had complete data. Four folate data (red blood cell folate, serum total folate, 5-methyl-tetrahydrofolate and folic acid) were included in our study. Controlled attenuation parameters (CAP) and liver stiffness came from the results of liver ultrasound transient elastography. We used linear regression to analyze the relationship between different forms of folate and CAP or liver stiffness, and logistic regression to analyze the relationship between different forms of folate and NAFLD or significant fibrosis. We also used restricted cubic splines to analyze the nonlinear relationship between different forms of folate and NAFLD or significant fibrosis. Finally, we used regression-based intermediary analysis to distinguish the direct and BMI-mediated effects of folate on CAP or liver stiffness. All the analyses adjusted the relevant covariates.ResultsThe means of CAP and liver hardness in this study were 223.02dB/m and 5.03kPa, respectively. We found that in model 2, there was a negative correlation between serum total folate (β: -18.53; 95%CI: -29.32 to -7.73) or 5-methyltetrahydrofolate (β: -14.13; 95%CI: -28.98 to -7.86) and CAP. However, when the BMI was further adjusted in model 3, this negative correlation no longer existed (serum total folate: β: -8.36; 95%CI: -17.69 to 0.97; 5-methyltetrahydrofolate: β: -8.05; 95%CI: -17.19 to 1.09). Similarly, we found a negative correlation between serum total folate or 5-Methyl-tetrahydrofolate and liver stiffness in model 2. There was no significant correlation between red blood cell folate or folic acid and CAP or liver stiffness in either model 2 or model 3. The nonlinear relationship between different folate forms and NAFLD or significant fibrosis was not significant. It is estimated that 76% of the total association between serum total folate and CAP is mediated by BMI. The mediating proportion of BMI in the total correlation between serum total folate and liver stiffness was 50%. Similarly, we found that BMI significantly mediated the relationship between 5-Methyl-tetrahydrofolate and CAP or liver stiffness, with a mediating ratio of 77% and 49%, respectively.ConclusionOur results show that serum total folate or 5-Methyl-tetrahydrofolate are negatively correlated with hepatic steatosis or liver stiffness in adolescents, and BMI plays major mediating role in this relationship. Our findings emphasize the importance of monitoring the concentration of serum folate, not just the serum total folate concentration.

Objective:To investigate the role of HIS (hyperinflammatory syndrome) score in predicting the prognosis of anti-melanoma differentiation associated gene 5(MDA5) antibody-positive dermatomyositis (DM) patients with interstitial lung disease (ILD).Methods:A total of 43 patients with anti-MDA5 antibody-positive dermatomyositis and 228 connective tissue disease (CTD) patients with ILD hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2018 to April 2021 were enrolled into this study. All patients were complicated with ILD and their HIS score were assessed. Non-parametric Mann-Whitney U test, Chi-squared test, Fisher exact probability and receiver operating characteristic (ROC) curve were used for data analysis. Results:The HIS score of 43 patients with anti-MDA5 antibody-positive dermat-omyositis were collected. Among 228 CTD-ILD patients in the control groups, the primary disease consisted of 33(14.5%) anti-synthetase antibody syndrome (ASS), 44(19.3%) rheumatoid arthritis (RA), 65(28.5%) Sj?gren's syndromes (SS), 43 (18.9%) systemic sclerosis (SSc) and 43 (18.9%) systemic lupus erythematosus(SLE). The HIS score of anti-MDA5-positive DM-ILD patients [2(1, 3)] was higher than those in ASS patients [1(0, 2), Z=-2.06, P<0.05] and significantly higher than those in RA-ILD [1(0, 2), Z=-2.87, P<0.01], SS-ILD [0(0,1), Z=-5.78, P<0.01], SSC-ILD [1(0, 1), Z=-3.84, P<0.01] and SLE-ILD [1(0, 2), Z=-3.81, P<0.01]. Comparing HIS score of anti-MDA5-positive DM-ILD patients, the 3-months mortality rate in the low, medium and high groups was 0(0/15), 38.1%(8/21) and 85.7%(6/7). The area under ROC curve (95% CI) was 0.857[(0.747, 0.967), P<0.001] for HIS score in predicting 3-months mortality probability of anti-MDA5-positive DM-ILD. Conclusion:HIS score of anti-MDA5-positive DM-ILD is higher than that in CTD-ILD patients and the baseline level is related to the 3-months mortality rate.

OBJECTIVES:Rapidly progressive interstitial lung disease (RP-ILD) is a major complication of anti-melanoma differentiation-associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) with a high mortality rate. The aim of the study is to determine whether serum Krebs von den Lungen-6 (KL-6) could be a prognostic biomarker to predict RP-ILD and prognosis in anti-MDA5+DM patients. METHODS:A total of 21 anti-MDA5+DM patients with RP-ILD and 20 anti-MDA5+DM patients without RP-ILD were retrospectively included in this study. Serum KL-6 concentration (pg/mL) was measured using the latex agglutination test. RESULTS:Serum KL-6 level was higher in RP-ILD patients than those in non-RR-ILD patients (1195.61±872.93 vs. 452.6±465.51 pg/mL, p=0.002). The best cut-off value of KL-6 serum level was 500.9 pg/mL using ROC curve (AUC area = 0.7976, p=0.0011). KL-6 >500.9 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR=56.38, 95% CI 5.51-577.504, p=0.001). Serum KL-6 concentrations were significantly higher in dead patients than those in the survivor group (1209.34±840.55 vs. 592.41±667.76, p=0.0033), and higher KL-6 concentration was also an independent risk factor for all-cause death after adjusting confounders (OR = 21.94, 95% CI 3.3-145.73, p=0.001). Anti-MDA5+DM patients with higher KL-6 level displayed a significantly decreased one-year survival rate, as compared with lower KL-6 level (36.36% vs. 89.47%, p=0.0008). CONCLUSIONS:The serum KL-6 levels reflect severity of lung injury and serve as a clinically useful biomarker in detection and monitoring RP-ILD progression in anti-MDA5+DM patients.

目的 分析小儿气管异物临床急救与护理体会.方法 将2019年5月～2020年10月我院接诊的31例气管异物患儿作为观察对象,全部患儿均行全麻下支气管镜异物检查+异物取出术,同时辅以护理干预,分析急救及护理效果.结果 全部31例气管异物患儿在接受及时的诊疗、急救与护理干预后,最终均痊愈出院,但术后共7例患儿出现并发症,并发症发生率为22.58％,包括2例喉头水肿(6.45％)、2例支气管炎(6.45％)、3例肺炎(9.68％).结论 有效的急救处理及护理干预,能够提高气管异物患儿治愈率,确保抢救成功,值得推广.

Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 eligible patients were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet’s disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p<0.001), taking azathioprine(AZA) within the past two years (OR=2.095, 95% CI: 0.986-4.450, p=0.054), exposing to glucocorticoids ≥30mg/d for more than four weeks within the past two years (OR=2.031, 95% CI: 1.247-3.309, p=0.004) and having evidences of previous TB (OR= 6.185, 95% CI: 3.487-10.969, p<0.001). The prevalence of ATB was higher in patients with rheumatic diseases compared to the general population. Patients with SLE or BD, prolonged exposure to moderate to high dose of glucocorticoids and previous TB were independent risk factors for ATB.

Background To investigate the association of a coronary artery disease (CAD) risk SNP rs6903956 with asymptomatic hyperuricemia (aHU) susceptibility in Han Chinese. Methods Two hundred and twenty one patients with aHU and 447 healthy controls were recruited for this study. SNP rs6903956 were genotyped using TaqMan probe. Results The overall genotype and allele frequency distribution of the rs6903956 showed significant difference between aHU cases and controls (p <0.001 for genotype and allele, respectively). AA genotype of rs6903956 was significantly associated with aHU (OR = 8.672, 95% CI 2.811-26.753, p <0.001) in our Han Chinese aHU cohort. Multivariate logistic regression analysis indicated that rs6903956 might be an independent risk factor for aHU susceptibility (OR = 10.642 [2.671- 42.400], p = 0.001 for codominant model and OR = 9.205 [2.336-36.280], p = 0.002 for recessive model) after adjustment for some well- known CAD risk factors including age, gender, body mass index, smoking, hypertension, diabetes mellitus, abnormal glycometabolism, lipid abnormality and alcohol intake. No significant genotype-specific difference in uric acid levels was observed in aHU patients and controls. Conclusions Our findings are the first to establish a genetic link of a CAD-associated rs6903956 with aHU in a Han Chinese population, providing the genetic evidence to support the close relationship between hyperuricemia and CAD.

Objective To investigate the expression of IL-7 in serum of patients with rheumatoid arthritis(RA) and to identify its clinical significance in RA.Methods The levels of IL-7 in serum were measured by enzyme-linked immunosorbent assay(ELISA)in 42 patients with RA,and 20 nomal controls.And their clinical significance was analysed with corresponding clinical materials.Results The serum IL-7 levels in severe RA patients were signficantly higher than that in mild RA patients(P=0.013)and normal controls(P=0.001).The optimal operating point of IL-7 was 1.72 pg/ml.There were significant correlations between serum IL-7 and CRP(r=0.437,P=0.048)and ESR(r=0.459,P=0.037).Conclusion IL-7 could serve as a supplemental parameter in diagnosing RA,especially in severe RA.It may help evaluate the disease activity of RA.

Objective To investigate the prevalence and risk factors of hyperuricemia (HUA) in rural residents of Gaoyou City,Jiangsu Province.Methods A total of 4504 rural residents were investigated in a cross-sectional study.Questionarre survey and physical examination were used for the stndy.Fatsing venous blood samples were collected for biochemical examination.T-test,chi-square test for multiple-group data comparison and logistic regression analysis were used for statistical analysis.Results The prevalence of HUA was 11.9％,15.7％ in male,which was significantly higher than 8.6％ in the female (P＜0.01),the risks of HUA in male was 1.98 times higher than in female.The average value of serum uric acid in this population was higher than.that of female.The prevalence of HUA in female increased with age.Non-conditional logistic regression analysis showed WHR,Cr,Tg,hypertension were the independent risk factors of male patients with HUA.Age,BMI,Cr,Tg,hypertension were independent risk factors of HUA in female.Conclusion The prevalence of HUA can be affected by age and sex.Weight control,keeping blood pressure and blood lipid profiles in normals levels are important for the prevention of HUA.

The purpose of this paper is to explore the five elements of CBD space, innovation presentation that future direction of development of Yangzhou CBD will be concentrated in the Jing hua Mall Circle, Wenchang Circle. Will also form a network-like multi-core and multi-sub-center commercial space development model. The theory is characterized by two aspects, spatial structure by pictures and charts from a single center to multi-center network, and translate superimposed imprint is intensive three-dimensional network. Finally for the five constituent elements of the physical CBD space corresponding to sum up the goals to create Yangzhou CBD space for superimposed imprints.

皮肌炎或多发性肌炎(dermatomyositis or polymyositis,DM/PM)是一种主要以骨骼肌非化脓性炎症为特征的自身免疫性炎性肌病,和多种恶性肿瘤的发生有关.为提高对DM/PM并发恶性肿瘤的认识,我们对近三年多来在我院住院的121例DM/PM患者临床资料进行分析总结,现报告如下.

Pyruvate kinase (PK; EC 2.7.1.40) is a key glycolytic enzyme of Drosophila melanogaster. It catalyzes the conversion of phosphoenolpyruvate into pyruvate with the transfer of a phosphate group to ADP to form ATP. The ATP provides energy for cell growth and metabolism, and pyruvate participates in many metabolic reactions. Therefore, PK plays an important role in cell metabolism. Southern blot analysis, PCR, and sequencing were used to determine the content of a Drosophila pyruvate kinase (Pyk) genomic clone, lambdaPK61. The results indicated that the insert of lambdaPK61 comprised 8330 bp upstream of and 7186 bp downstream of the transcription start point of the Pyk gene. The size of the insert was 15,516 bp in total, which contained six genes including Pyk. Deletion mapping was applied to identify the promoter region and cis-acting elements 5' of PyK. Ten serial deletions produced by PCR were inserted upstream of the reporter gene (LacZ) to form recombinant plasmids, which were then transfected into Drosophila S2 cells. The results revealed that the regions -1475 approximately -1033 and -1033 approximately -534 of the 5' end of PyK possessed positive regulatory function for Pyk expression; i.e., increased gene expression. There were redundant putative cis-acting elements, including ecdysone response element (EcRE), E74A, and broad complex zinc finger (BRCZ) binding sites. Both E74A and BRCZ belong to the early genes regulated by ecdysone. This result suggested that Pyk might be regulated by ecdysone, directly or indirectly. However, the results of the developmental profile of Pyk expression by Northern blot analysis suggested that the effects of ecdysone on Pyk were repressive, not inductive. In addition, it was found that in these regions, there were many cis-acting elements related to egg and embryo development. Both -258 approximately -254 and -167 approximately -163 contained a CAAT box, and deletion of these regions decreased reporter gene expression. Therefore, it is suggested that both CAAT boxes are functional and that the promoter of Pyk might be located in the region of -258 approximately +109. No TATA box or downstream promoter element were identified around the transcription start site of Pyk. Additionally, PyK might share a regulatory region with an unknown neighboring gene. It was concluded that Pyk has the characteristics of a housekeeping gene.

Screening a lambda-gt10 cDNA library of Drosophila melanogaster using a human pyruvate kinase (Pyk) cDNA clone (pCJ11) and a rat pituitary Pyk cDNA clone (pCJ22) as probes, we isolated 2 cDNA clones, cDMPK15 and cDMPK06. Complete nucleotide sequencing of the two cDNA clones (GenBank AF061507) revealed that they encompassed the coding region of pyruvate kinase cDNA (1602 bp; 533 amino acids + TAA) flanked by a 5' untranslated region of 240 bp and a 3' untranslated region of 253 bp. An alignment of the deduced amino acid sequence from the Pyk cDNA clones with those of PK from other organisms indicated that the amino acid residues constituting the active sites have been highly conserved. In addition, the overall positional identity between the sequence of the "Drosophila" enzyme and those from other sources was 42%-63%.Polymerase chain reaction was applied to amplify the genomic DNA fragments from the Pyk gene of D. melanogaster. These overlapping amplicons, which covered the complete coding region of Pyk, were further sequenced using cycle-sequencing with an ABI Prism 377 DNA sequencer. A total of 3447 bp of the nucleotide sequence (GenBank AF062478) was determined from these amplicons. By comparing these sequences with the sequence of Pyk cDNA clones isolated, 4 exons were identified of 282, 1390, 157, and 266 bp in length. The introns identified all contained the consensus 5'- and 3'-splicing sites (GT-BG). RT-PCR analysis was performed to determine the number of species of the Pyk transcript in adults of D. melanogaster. The observation that only a single amplicon appeared in each amplification suggests that a single Pyk transcript is expressed in adults of D. melanogaster, and might imply that there is only 1 Pyk gene in D. melanogaster.