Abstract Background: Previous studies have observed a significant association between immune cell traits and Ankylosing spondylitis (AS); however, a causal relationship has not been established. Therefore, we conducted this bidirectional Mendelian randomization study to comprehensively evaluate the intricate interactions between 731 immune cell traitsand AS, aiming to uncover potential causal relationships while enhancing our understanding of disease development. Methods: We retrieved extensive genome-wide association study (GWAS) data from two reputable sources, the IEU open GWAS database and the FinnGen studies, renowned for their extensive genetic information. We performed a bidirectional Mendelian randomization study to investigate the causal relationship between 731 immune cell traits and Ankylosing Spondylitis (AS). Our analysis utilized the Inverse Variance Weighted (IVW) method, along with MR-Egger, Weighted Median, and Weighted Mode. We assessed associations between 731 immune cell traits and AS using odds ratios (OR) and 95% confidence intervals (CI). Finally, we performed tests for horizontal pleiotropy, heterogeneity, and conducted a leave-one-out sensitivity analysis to validate our results. Results: Our research has established that 10 distinct immune cell types significantly contribute to the development of Ankylosing Spondylitis (AS). We identified 3 types of monocytes, 1 type of T cell, 1 type of B cell, and 1 type of granulocyte as risk factors for AS. In contrast, a different group of immune cells, including 1 type of monocyte, 2 types of T cells, and 1 type of B cell, appears to offer protection against the disease. Concerning the onset of AS, its impact on immune traits is evident in the varied expressions across 41 T cell subgroups: 16 subtypes show high expression, while 25 demonstrate low expression. Similarly, in B cells, 3 subtypes are highly expressed, and 4 subtypes are lowly expressed. Likewise, variations in expression were observed in lymphocytes and monocytes, with 3 types of each showing high and low expression, respectively. Moreover, our study reveals a bidirectional causal relationship between the expression of CX3CR1 on CD14+ CD16- monocytes and on monocytes generally, and the occurrence of AS. Conclusion: The goal of this research is dedicated to exploring the bidirectional causal relationship between immune cells traits and Ankylosing Spondylitis (AS). It aims to not only offer new avenues for unraveling the biological mechanisms of AS but also to guide clinical research towards novel investigative directions and to provide fresh clues for the development of new therapeutic approaches.

Background. Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are prevalent autoimmune disorders that often co-occur, posing significant treatment challenges. This investigation adopts a multidisciplinary strategy, integrating bioinformatics, network pharmacology, molecular docking, and Mendelian randomization, to elucidate the relationship between AS and IBD and to investigate the potential mechanisms of traditional Chinese medicine formulations, represented by Qiangji Jianpi (QJJP) decoction, in treating these comorbid conditions. Methods. We utilized databases to pinpoint common targets among AS, IBD, and QJJP decoction’s active compounds through intersection analysis. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we mapped a network in Cytoscape, isolating critical targets. Molecular docking with AutoDock validated the affinity between targets and compounds. ROC analysis and dataset validation assessed diagnostic performance, while Gene Set Enrichment Analysis (GSEA) offered pathway insights. Mendelian randomization explored the AS-IBD causal relationship. Results. Screening identified 105 targets for QJJP decoction, 414 for AS, and 2420 for IBD, with 85 overlapping. These targets predominantly participate in organismal responses and DNA transcription factor binding, with a significant cellular presence in the endoplasmic reticulum and vesicle lumen. Molecular docking, facilitated by Cytoscape, confirmed IL1A, IFNG, TGFB1, and EDN1 as critical targets, with IFNG demonstrating diagnostic potential through GEO dataset validation. The integration of GSEA with network pharmacology highlighted the therapeutic significance of the relaxin, osteoclast differentiation, HIF-1, and AGE-RAGE signaling pathways in QJJP decoction’s action. Mendelian randomization analysis indicated a positive causal relationship between IBD and AS, pinpointing rs2193041 as a key SNP influencing IFNG. Conclusion. Based on the principle of “treating different diseases with the same method” in traditional Chinese medicine theory, we explored the intricate mechanisms through which QJJP decoction addresses AS and IBD comorbidity. Our research spotlighted the pivotal role of the IFNG gene. IFNG emerges not only as a key therapeutic target but also assumes significance as a potential diagnostic biomarker through its genetic underpinnings. This investigation establishes a solid base for subsequent experimental inquiries. Our findings introduce novel approaches for incorporating traditional Chinese medicine into the treatment of AS-IBD comorbidity, setting the stage for groundbreaking research directions.

Background Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are both autoimmune diseases, and they often occur together in clinical practice, but the pathogenesis is unclear. This study is aimed at identifying the hub genes and explore the related immune molecular mechanisms between AS and IBD by bioinformatics analysis. Methods From the public Gene Expression Omnibus (GEO) database, the AS and IBD datasets (GSE73754, GSE59071, GSE25101, and GSE36807) were obtained. The immune cell infiltration in the peripheral blood tissues of GSE73754 and GSE59071 was assessed using the CIBERSORT algorithm. Then, we used the Weighted Gene Coexpression Network Analysis (WGCNA) to identify the Differentially Expressed Genes (DEGs) related to AS and IBD. Then, the immune genes from the ImmPort database intersected with the DEGs to obtain hub genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the functional correlation of hub genes. Then, hub genes were verified in GSE25101 and GSE36807. The clusterProfiler software and Gene Set Enrichment Analysis (GSEA) were used to conduct functional enrichment and pathway enrichment studies. Finally, the diagnostic efficacy was assessed using Receiver Operating Characteristic (ROC) curve analysis. Results The analysis of immune characteristics showed that both AS and IBD were related to immunity, and neutrophils were positively correlated in both diseases. Nine coexpressed genes, including FCGRT, S100A11, IFNGR1, NFKBIZ, JAK2, LYN, PLAUR, ADM, and IL1RN, were linked to immune cells. The GO and KEGG analyses results showed that enrichment analysis was mainly related to cell transport and migration. Finally, the ROC curve was verified with the validation set, and it was found that PLAUR has clinical diagnostic significance and the most excellent specificity and sensitivity, respectively. Conclusions PLAUR (uPAR) is a promising biomarker and will be an underlying genetic biomarker for diagnosing AS comorbid IBD. Inflammation and immunological modulation mediated by neutrophil infiltration were important in the development of AS and IBD and may be diagnostic and therapeutic targets.

To explore the etiology of risk factors and quantify the mortality differences in systemic lupus erythematosus (SLE) patients with different initial disease activity. The Jiangsu Lupus database was established by collecting medical records from first-hospitalized SLE patients during 1999–2009 from 26 centers in Jiangsu province, China, and their survival status every five years. The initial SLEDAI scores [high (>12) vs. low–moderate (≤12)] differences in mortality attributable to risk factors were quantified using population attributable fraction (PAF), relative attributable risk (RAR) and adjusted relative risk (ARR). Among 2446 SLE patients, 83 and 176 deaths were observed in the low–moderate and high activity groups, with mortality rates of 7.7 and 14.0 per 1000 person years, respectively. Anemia was the leading contributor to mortality, with PAFs of 40.4 and 37.5 in the low–moderate and high activity groups, respectively, and explained 23.2% of the mortality differences with an ARR of 1.66 between the two groups. Cardiopulmonary involvement caused the highest PAFs in the low–moderate (20.5%) and high activity (13.6%) groups, explaining 18.3% of the mortality differences. The combination of anemia and cardiopulmonary involvement had the highest RAR, causing 39.8% of the mortality differences (ARR = 1.52) between the two groups. In addition, hypoalbuminemia and a decrease in the creatinine clearance rate accounted for 20–30% of deaths and explained 10–20% of the mortality differences between the two groups, while antimalarial drug nonuse accounted for about 35% of deaths and explained 3.6% of the mortality differences. Anemia, cardiopulmonary involvement and hypoalbuminemia may cause substantial mortality differences across disease activity states, suggesting additional strategies beyond disease activity assessment to monitor SLE outcomes.

To analyze the relative factors of improvement in disease activity (IDA) after first hospitalized treatment based on the systemic lupus erythematosus disease activity index (SLEDAI). A total of 1069 adult systemic lupus erythematosus (SLE) patients who were hospitalized for the first time in 26 hospitals in Jiangsu Province from 1999 to 2009 were retrospectively analyzed. SLEDAI decrease ≥ 4 during hospitalization was identified as IDA. Relative factors of IDA were assessed by univariate and multivariate logistic regression. A total of 783 (73.2

Background The aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status. Methods In this study, based on 1999–2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients’ survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression. Results The overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment. Conclusions The proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions.

Background: Cyclophosphamide (CTX) is an alkylating agent used in the treatment of systemic lupus erythematosus (SLE) for its potent immunosuppression effect. Many aspects of the use of CTX in SLE have been previously studied. However, its relation to mortality in SLE had rarely been mentioned. Thus we investigate the effect of cyclophosphamide on organ involvements and the overall and cause-specific mortality of SLE patients. Methods: Information about CTX prescription were taken from medical records in the Jiangsu Lupus database that was set up to collect data from SLE patients since their first admission during 1999-2009 in Jiangsu province, China. Follow- up studies were carried out in 2010 and 2015 to check the survival status of the patients. Cox regression models were used to estimate hazard ratio (HR) and 95% CI. Kaplan-Meier model was used to assess the effect of CTX on mortality between organ involvements and non-involvements. Results: There were 221 deaths observed out of 2446 SLE patients. CTX users showed a lower mortality of SLE (8.4%) with adjusted HR (95% CI) of 0.74 (0.56-0.97), as compared to non-users. A decreased in overall mortality of SLE in low daily dosage of CTX, with adjusted HR (95% CI) of 0.54 (0.36-0.81) and a significant dose-response pattern ( P = 0.004) between overall mortality of SLE and long-term use of CTX with adjusted HR (95% CI) 0.53 (0.35-0.80) were observed. In cause-specific mortality analyses, protective effective of CTX was found to be insignificant. However, CTX could eliminate the differences in mortality between organ involvement and non-involvement, including renal, neuropsychiatric, cardiopulmonary, gastrointestinal and hematological involvements. Conclusion: Low daily dosage and long-term use of CTX lowers the risk of overall mortality of SLE. CTX might improve the survival of patients with renal, neuropsychiatric, cardiopulmonary, gastrointestinal and hematological involvements.

干燥综合征属"燥证""燥痹"范畴,金实教授认为本病病位在肺、胃、肝、肾,以肺为主,属本虚标实之证,主要病机是肺失宣布、阴虚络滞,病因关键是肺不布津、脉络滞涩.治疗上强调宣肺布津,根据疾病的发生发展以及兼症的不同,进行化裁加减,初期滋阴润燥,后期久病及肝肾,注重滋补肝肾,贯穿燥证的过程中,强调了通络化滞的治疗.

A one-step ELISA has been developed for detection and serotyping of infectious pancreatic necrosis virus (IPNV) in infected cell cultures using monoclonal antibodies (mAb) raised against strains representing the Sp, Ab and VR 299 serotypes of IPNV. This assay uses a serotype-specific mAb as capture and a mAb directed against a common epitope as detector antibody. Avidin-peroxidase was employed for amplification. The assay was performed in 90 min by simultaneous incubation of the samples, the biotin labelled mAb and the avidin-peroxidase, and detected 37 ng/ml of purified virus. Serotyping of 34 isolates from different areas of Europe, Asia and America showed a total concordance with the results obtained by the neutralization assay.

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO 2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.

OBJECTIVETo evaluate the association and dose-response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients.METHODSMedical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999-2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI.RESULTSWe identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose-response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements.CONCLUSIONAntimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.

Introduction A considerable proportion of patients with systemic lupus ery­thematosus (SLE) have liver enzyme abnormalities. We evaluated whether fibrosis-4 (FIB-4) was associated with increased mortality of SLE patients. Material and methods A multicenter retrospective cohort study was conducted based on medical records of first-admission SLE patients who were hospitalized during 1999–2009 in Jiangsu province. FIB-4 was estimated by age, platelet (PLT) count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and FIB-4. A Cox model and a restricted cubic spline (RCS) model were used to estimate hazard ratio (HR) and 95% confidence interval (95% CI). Results During up to 15 years of follow-up, 226 deaths were observed among 2331 SLE patients. Increased overall mortality was associated with abnormal groups of PLT, ALT, AST, and high FIB-4 (≥ 1.92), with adjusted HRs (95% CI) of 1.58 (1.19–2.11), 1.54 (1.14–2.07), 1.58 (1.17–2.12), and 1.88 (1.42–2.50), respectively. Moreover, significant dose-response relationships were found between mortality of SLE and those indexes, and it was nonlinear for PLT (p < 0.001), ALT (p = 0.046) and FIB-4 (p < 0.001), but not AST (p = 0.109). In cause-specific analyses, high FIB-4 index was directly associated with death from liver failure and indirectly associated with other death from infection and neuropsychiatric impairment. We found no significant differences of areas under curves (AUCs) between FIB-4 index and the disease activity index score of SLE. Conclusions This is the first report to describe the nonlinear association between FIB-4 index and increased mortality of SLE patients. The FIB-4 index may be used as an independent prognostic indicator for SLE patients.

To explore the association between the creatinine clearance rate (Ccr) and the prognosis of patients, and compared with estimated glomerular filtration rate (eGFR). We retrospectively collected information of patients with SLE who were first hospitalized between 1999 and 2009 in Jiangsu Province, China, and followed up in 2010 and 2015. Ccr was calculated and dichotomized into normal group (Ccr ≥ 70) and decreasing group (Ccr < 70). The clinical characteristics of the two groups were compared and Cox proportional-hazards regression models were used to calculate hazard ratio (HR) and 95% confidence interval (CI). Among 1990 SLE patients, we observed 437 (22.0%) with decreased Ccr, including 237 cases (11.9%) with mild renal dysfunction, 136 cases (6.8%) with moderate renal dysfunction, and 64 cases (3.2%) with severe renal dysfunction. Compared to normal Ccr, decreasing Ccr had a higher risk for mortality with adjusted HR (95% CI) of 2.21 (1.59–3.06). Dose-response relationships were significantly found between increased mortality of SLE and decreased Ccr (p for trend < 0. 001), as well as eGFR. Positive associations were consistently observed in subgroups, such as systemic lupus disease activity index (SLEDAI) ≥ 15, without comorbidities and abnormal laboratory indexes. Decreasing Ccr was positively associated with mortality from infection and renal failure with HR (95% CI) of 1.80 (1.02–3.19) and 6.84 (3.05–15.36). A significant association has been observed between decreased Ccr and increased risk for mortality of SLE patients. Early clinical interventions to modulate the Ccr of SLE patients may be beneficial to their survival.

糖尿病是一组以慢性血葡萄糖水平增高为特征的代谢性疾病.现代医学认为此病的发生是由于胰岛素分泌或缺陷引起.疾病发展可逐渐导致眼、肾脏、神经、血管等多系统损害.现代中医将其与古代典籍中消渴病相对应.并将其分为上消、中消、下消分型治之[1].

强直性脊柱炎属"大偻""骨痹"等范畴,钱先教授认为本病病位在肾与脊柱,和肝、脾胃密切相关,属本虚标实之证,本虚为肾虚督空,标实为风、寒、湿、热、痰、瘀痹阻经络.治疗应分期而治,疾病初期应注重祛风除湿,散寒通络,疾病中期根据兼证的不同,选用不同治法;疾病后期注重化痰袪瘀,但在疾病的各个时期都主张补肾强督为治疗基本原则,并重视炎性肠病和葡萄膜炎等兼夹证的治疗.

白塞病,中医称之为"狐惑病".张仲景《金匮要略》对其有较详细的论述,认为狐惑病乃湿热化生虫毒所致,应以甘草泻心汤为主方,治疗上以清热燥湿、和中解毒为原则.钱先教授结合《金匮要略》指导现代白塞病的治疗.认为初期病机为湿热内蕴,疮毒内扰,治以清热燥湿,和中解毒,方用张仲景《金匮要略》之甘草泻心汤加减;后期湿毒不化,目黑酿脓,治以《金匮要略》之赤小豆当归散清热利湿、行瘀排脓.外治方面:前阴溃疡可用苦参汤外洗,后阴溃疡可用雄黄熏之.

目的:探讨强直性脊柱炎(AS)中医辨证分型与C反应蛋白(CRP)、血沉(ESR)、骶髂关节炎的相关性,为AS中医辨证分型提供参考依据.方法:收集AS住院病例资料及CRP、ESR、骶髂关节炎CT检测结果,中医辨证分4型:肾虚督寒证、湿热痹阻证、痰瘀阻络证、肝肾亏虚筋骨失荣证,比较其炎性反应与中医辨证分型之间的关系.结果:共收集AS确诊病例367例,其中肾虚督寒证52例,湿热痹阻证65例,痰瘀阻络证86例,肝肾亏虚筋骨失荣证150例,其他证型14例,湿热痹阻证型CRP、ESR显著高于肝肾亏虚筋骨失荣证(P＜0.01,P＜0.05),肾虚督寒证与痰瘀阻络证及肝肾亏虚筋骨失荣证间CRP、ESR差异无统计学意义.骶髂关节炎CT分级,湿热痹阻证显著低于肾虚督寒证、痰瘀阻络证及肝肾亏虚筋骨失荣证(P＜0.05,P＜0.01),余各组之间数据差异无统计学意义.结论:不同中医证型AS的炎症程度分布存在一定差异,CRP、ESR、骶髂关节炎CT分级可为AS的中医分型提供参考依据.

In conclusion, our data show that the use of antimalarials could improve long-term outcome of Chinese patients with SLE.These drugs possess protective effects on a wide range of clinical aspects.Patients with vital organ involvements, especially cardiopulmonary, gastrointestinal, renal or haematological impairments, may gain more benefits from antimalarial treatments.

Systemic sclerosis (SSc) is a rare chronic autoimmune disorder, mainly characterized by skin sclerosis. In this study, Bufei Qingyu Granules (BQG), a Chinese herbal formula, was used to treat SSc. To better understand the effects and molecular mechanisms of BQG, we successfully established a Bleomycin- (BLM-) induced SSc mouse model, and the mice were treated by BQG. Meanwhile, transcriptomic and bioinformatics analyses were conducted on those samples. As a result, we visually showed that BQG ameliorated the overall health of mice, including body weight, spleen, and thymus index. Thus, it also significantly alleviated inflammation presented by Chemokine (C-X-C motif) ligand 2 (Cxcl2), vasculopathy characterized by α -smooth muscle actin ( α -SMA), and fibrotic changes elaborated by not only pathological images, but also the hydroxyproline (HYP) content. After testing by transcriptomic analysis, Cxcl2, Synaptosomal-associated protein 25 (Snap25), and Eukaryotic translation initiation factor 3, and subunit J2 (Eif3j2) which were differentially expressed genes, were verified, so that the data were credible. We further found that BQG could regulate Notch signaling pathway by significantly decreasing both mRNA and protein expression levels of Notch-1 and Jagged-2. Hence, this study demonstrated that BQG could ameliorate the sclerotic skin in mice model involved in inflammation, vascular changes, and fibrosis effects, which was partly mediated by Notch signaling pathway.

Fibrosis is the characteristic hallmark of systemic sclerosis (SSc). Although the specific mechanism has been unknown, the role of macrophages in the development of this complex disease through various ways cannot be negligible. Findings during the past 5 years have contributed to more understanding of the relationship between macrophages and SSc. This review is mainly about the progress of research on macrophages in SSc. We discuss whether or not macrophages skew toward the M1-like phenotype from the profibrotic M2-like phenotype. Some biomarkers are also listed. In addition, we elaborate on the association of macrophages with other immune cells and Tall-like receptors.