Systemic lupus erythematosus associated with sarcoidosis: Case report

BackgroundThe association between systemic lupus erythematosus (SLE) and sarcoidosis has been considered as extremely rare. Most often, sarcoidosis coexists with Sjögren's syndrome. Researching the literature, it seems that the association of SLE and sarcoidosis is much more frequent than previously thought.Aim of the workWe present a case of a Serbian woman who was diagnosed with coexisting sarcoidosis and long-standing SLE.Case presentationThe 40 years old SLE patient was in long-standing remission on oral prednisolone (10 mg/day) and hydroxychloroquine (HCQ) (400 mg/day). She presented with fatigue, chest pain, and dry cough. Chest computerized tomography (CT) showed hilar and mediastinal lymphadenopathy. The biopsy had been performed and results showed sarcoidosis. Diagnosis has been confirmed: eosinophilic granulomas without central necrosis morphologically corresponding to chronic granulomatous lymphadenitis like sarcoidosis. Thereafter, the patient was hospitalized. No new symptoms appeared, and the physical examination was unremarkable. Serum calcium was elevated (2.75 mmol/l), anti-nuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-dsDNA) and anti-Ro antibodies were positive. Angiotensin converting enzyme (ACE) level was high normal (51 IU/L) and QuantiFERON-TB Gold test negative. The dose of prednisolone was increased to 40 mg/day with HCQ and the patient was discharged from hospital. On follow-up the patient improved with reduction of the steroid dose.ConclusionThe association of SLE and sarcoidosis should be considered even though it is reported to be extremely rare. May be the real incidence of these combinations is underestimated. More research about genetics and pathogenesis is needed to completely understand these conditions.     

基于真实世界数据探讨中医药治疗糖尿病肾病用药规律的研究＊

目的 基于临床信息系统分析总结真实世界的数据，采用数据挖掘的方法探讨中医药治疗糖尿病肾病的用药规律。方法 收集2018年1月-2020年12月上海中医药大学附属曙光医院宝山分院健康信息系统确诊的糖尿病肾病的门诊或住院患者的诊疗信息，建立Excel数据库，采用Excel 2010软件统计高频药物的四气、五味、归经及功效；使用SPSS Modeler 18.0软件中的Apriori算法分析关联规则，采用web节点建构药对关联网状图；运用SPSS 25统计软件进行因子分析。结果 本研究最终纳入477例接受中药饮片治疗的DKD患者，在1203条方剂信息中，涉及中药462种；使用频数排名前5位的中药分别是黄芪、黄精、石斛、山茱萸、麦冬；使用频数前5类的中药类别分别是补气药、补阴药、清热燥湿药、活血调经药、息风止痉药；在30味高频药物中，苦、甘、辛药味最为常见；药性寒、温数量接近；归脾经、肝经、肺经、肾经居多；关联规则提示，药物组合中置信度最高的组合为地龙-当归-僵蚕，因子分析共得到5个有效因子，累积贡献率为47.33%。结论 中医药治疗DKD在补益气血阴阳的同时，兼顾对瘀血、湿邪和痰饮的治疗，结合证型，可考虑使用黄芪、黄精、石斛、山茱萸、麦冬、金蝉花等药物的使用，清热燥湿药物如黄连、黄芩、黄柏可适当加入，为使邪有去处，大黄、车前子或可增添疗效。     

Identification of key genes and pathways in discoid lupus skin via bioinformatics analysis

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets {"type":"entrez-geo","attrs":{"text":"GSE52471","term_id":"52471"}}GSE52471 and {"type":"entrez-geo","attrs":{"text":"GSE72535","term_id":"72535"}}GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.     

基于“通肾络、益脾肾”治法研究足细胞凋亡及自噬

[目的]基于中医"通肾络、益脾肾"治法,探讨通络益肾方对体外高糖培养的小鼠肾小球足细胞自噬和凋亡蛋白SIRT1、BNIP3、P62、Bax表达的调控影响。[方法]成熟无特定病原体(SPF)级SD雄性大鼠40只,随机分为正常组、中药高、中、低剂量组各10只。按照人与大鼠体表面积折算方法计算出大鼠所需中药灌胃浓度:高剂量浓度4.76 g/mL、中剂量浓度2.38 g/mL、低剂量浓度1.19 g/m L,灌胃10 d取含药血清备用。足细胞分6组,正常组5.6 mmol/L葡萄糖+10%正常大鼠血清、高糖组30mmol/L葡萄糖+10%正常大鼠血清、通络益肾方含药血清高、中、低干预组30 mmol/L葡萄糖+10%高、中、低剂量大鼠血清、高渗组甘露醇24.5 mmol/L+10%正常大鼠血清。细胞培养48 h后收集,Hoechst33342荧光染色,观察各组足细胞凋亡状况及形态变化;流式细胞仪检测足细胞凋亡率;Western Blot检测细胞内自噬标志蛋白SIRT1、P62及促凋亡蛋白BNIP3、Bax表达水平。[结果]流式细胞仪检测结果显示通络益肾方中、低剂量组可降低高糖诱导的足细胞凋亡率(P0.01或P0.05),高剂量组不能改善凋亡情况(P0.05);Hoechst33342荧光染色观察结果也证实通络益肾方中、低剂量组可降低高糖诱导的足细胞凋亡率;蛋白印迹结果显示,与高糖组相比,通络益肾方中、低剂量组自噬标志蛋白SIRT1表达升高,自噬标志蛋白P62及促凋亡蛋白BNIP3、Bax蛋白表达下降(P0.05或P0.01),高剂量组SIRT1、BNIP3、P62、Bax蛋白表达未见明显改变(P0.05)。[结论]中剂量、低剂量通络益肾方能够启动细胞自噬减少高糖刺激下体外培养足细胞凋亡,降低细胞凋亡率及凋亡蛋白的表达。     

辨证论治联合西药治疗IgA肾病的临床研究

目的研究辨证分型联合西药治疗免疫球蛋白a(Ig A)肾病的临床效果。方法选取收治的74例Ig A肾病患者,采用均衡分组法分为西药组和联合组,各37例。西药组采用氯沙坦钾片治疗,联合组辅以辨证分型治疗,治疗6个月后开展随访观察疗效。结果联合组治疗总有效率94.59%高于西药组的64.86%,联合组并发症发生率2.70%低于西药组的21.62%,联合组不良反应发生率2.70%低于西药组的24.32%,对比差异有统计学意义(P<0.05)。治疗后,联合组血肌酐高于西药组和治疗前,尿红细胞、尿蛋白指标低于西药组和治疗前,对比有统计学意义(P<0.05)。结论辨证分型联合西药治疗Ig A肾病的临床效果显著,可降低并发症及不良反应发生风险,改善其血液指标,具有较高临床推广价值。     

Neutrophil proteases degrade autoepitopes of NET-associated proteins

Neutrophils can form neutrophil extracellular traps (NETs) to capture microbes and facilitate their clearance. NETs consist of decondensed chromatin decorated with anti-microbial proteins. Here, we describe the effect of neutrophil proteases on the protein content of NETs. We show that the neutrophil serine proteases degrade several neutrophil proteins associated with NETs. Interestingly, the anti-bacterial proteins associated with NETs, such as myeloperoxidase, calgranulin B and neutrophil elastase (NE), seem to be less susceptible to proteolytic degradation than other NET proteins, such as actin and MNDA. NETs have been proposed to play a role in autoimmune reactions. Our data demonstrate that a large number of the autoepitopes of NET proteins that are recognized by autoantibodies produced by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients are also removed by the proteases. In conclusion, neutrophil serine proteases have a major impact on the NET proteome and the proteolytic changes of NET-associated proteins may counteract autoimmune reactions to NET components.     

The association between the decreased expression levels of FOXJ1 and the activation of NF-κB pathway in interstitial lung disease of MRL/Lpr mice

Background: Pulmonary manifestations of systemic lupus erythematosus (SLE) are appearing in 4-5% of patients involving lung in almost half of the cases during the disease course. Objective: We compared the autoimmune pulmonary inflammation in the lung tissue of mice to determine the association between decreased expression levels of Forkhead Box J1 (FOXJ1) and the activation of the NF-κB pathway in autoimmune pulmonary inflammation of MRL/Lpr mice. Methods: The female BALB/c mice (n=6) and MRL/Lpr mice (n=30) were divided into 5 groups including a control group (BALB/c), and five MRL/Lpr mice groups (8W, 12W, 16W, 24W, and 32W). The infiltration of the inflammatory cells was determined in lung tissue by performing the histological analysis. The western blotting was used to examine the expression levels of the age-related FOXJ1, and p50 and p65 proteins in the lungs of MRL/Lpr mice. The expression levels of MMP2 and MMP9 were determined via immunohistochemistry and immunofluorescence. Results: There were severe infiltrates of lung cells with high levels of tracheal damage, perivascular injury and interstitial inflammatory cell infiltration when the MRL/Lpr mice from 16w to 32w comparing to the 8w old healthy MRL/Lpr mice in the control group (p <0.05). Moreover, the reduced expression levels of FOXJ1 were associated with the activation of the NF-κB pathway in interstitial lung disease of MRL/Lpr mice via the modulation of p50 and p65. In addition, the expression levels of MMP2 and MMP9 pro-inflammation factors increased in the lungs of the MRL/Lpr mice from 16w to 32w. Conclusions: The expression level of FOXJ1 might be an indicator of the degree of lung disease in lupus-prone mice.