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Background Hypertension occurred in 30–80% of Takayasu arteritis (TAK) patients around the world and the occurrence of hypertension might worsen the disease prognosis. This study aimed to investigate the clinical characteristics and imaging phenotypes, as well as their associations with events free survival (EFS) in Chinese TAK patients with hypertension. Methods This current research was based on a prospectively ongoing observational cohort-the East China Takayasu Arteritis (ECTA) cohort, centered in Zhongshan Hospital, Fudan University. Totally, 204 TAK patients with hypertension were enrolled between January 2013 and December 2019. Clinical characteristics and imaging phenotypes of each case were evaluated and their associations with the EFS by the end of August 30, 2020, were analyzed. Results Severe hypertension accounted for 46.1% of the entire population. Three specific imaging phenotypes were identified: Cluster 1: involvement of the abdominal aorta and/or renal artery (27.5%); Cluster 2: involvement of the ascending aorta, thoracic aorta, the aortic arch, and/or its branches (18.6%); and Cluster 3: combined involvement of Cluster 1 and 2 (53.9%). Clinical characteristics, especially hypertensive severity, differed greatly among the three imaging clusters. In all, 187 patients were followed up for a median of 46 (9–102) months; 72 events were observed in 60 patients (1–3 per person). The overall blood pressure control rate was 50.8%, and the EFS was 67.9% by the end of the follow-up. Multivariate Cox regression indicated that controlled blood pressure (HR = 2.13, 95% CI 1.32–3.74), Cluster 1 (HR = 0.69, 95% CI 0.48–0.92) and Cluster 3 (HR = 0.72, 95% CI 0.43–0.94) imaging phenotype was associated with the EFS. Kaplan–Meier curves showed that patients with controlled blood pressure showed better EFS (p = 0.043). Furthermore, using cases with Cluster 1 imaging phenotype and controlled blood pressure as reference, better EFS was observed in patients with Cluster 2 phenotype and controlled blood pressure (HR = 2.21, 95%CI 1.47–4.32), while the case with Cluster 1 phenotype plus uncontrolled blood pressure (HR = 0.64, 95%CI 0.52–0.89) and those with Cluster 3 phenotype and uncontrolled blood pressure (HR = 0.83, 95%CI 0.76–0.92) suffered worse EFS. Conclusion Blood pressure control status and imaging phenotypes showed significant effects on the EFS for TAK patients with hypertension.

Objectives In IgG4-related disease, the relationship between pathological findings and relapse has not been well established. This study aimed to identify the clinical and pathological predictors of disease relapse in IgG4-RD. Methods Patients with newly diagnosed IgG4-RD (n = 71) were enrolled between January 2011 and April 2020; all cases were pathologically confirmed. The clinical and pathological features were recorded in a database at baseline and each follow-up visit. Patients were followed up at least once a month via outpatient clinic examinations and telephone calls. Univariate and multivariate Cox regression analyses and receiver operating curve (ROC) analysis were used to identify the predictors of disease relapse and to assess their predictive value. Results Over a median follow-up of 26 (range, 6–123) months, 3/71 (4.2%) patients died. Of the remaining 68 patients, 47 (69.1%) patients had achieved clinical remission and 21 (30.9%) had suffered relapse at the last follow-up. The independent predictors of relapse were IgG4 ≥ 6.5 g/L (HR = 2.84, 95% CI: 1.11–7.23), IgG ≥ 20.8 g/L (HR = 4.11, 95% CI: 1.53–11.06), IgG4-RD responder index (RI) ≥ 9 (HR = 3.82, 95% CI: 1.28–11.37), and severe IgG4+ plasma cell infiltration (HR = 6.32, 95% CI: 1.79–22.41). A prognostic score developed using three of the identified predictors (IgG ≥ 20.8 g/L, IgG4-RD RI ≥ 9, and severe IgG4+ plasma cell infiltration) showed good value for predicting impending relapse (AUC, 0.806). Conclusions In patients with IgG4-RD, IgG4 ≥ 6.5 g/L, IgG ≥ 20.8 g/L, IgG4-RD responder index (RI) ≥ 9, and severe IgG4+ plasma cell infiltration are predictors of relapse.

Additional file 1: Supplementary Figure 1. Flow chart depicting the study design. Supplementary Figure 2. Gating strategies in flow cytometry for peripheral immune subsets analysis. Supplementary Figure 3. Results of chemokine array in the present study. Supplementary Figure 4. Vascular infiltration in patients with TAK. Supplementary Figure 5. Peripheral cytokine levels and their correlation with chemokine levels in patients with TAK. Supplementary Figure 6. Correlations between chemokines and disease activity markers in patients with TAK. Supplementary Figure 7. Correlations among different chemokines and changes in their levels after treatment. Supplementary Table 1. Clinical characteristics of the patients included for vascular tissue examination. Supplementary Table 2. Key functions of the five major chemokines.

Supplemental material, sj-docx-1-taj-10.1177_20406223221127237 for Risk factors of aortic regurgitation progression in Chinese patients with Takayasu’s arteritis: a prospective cohort study by Yujiao Wang, Lili Ma, Ying Sun, Wensu Yu, Sifan Wu, Huiyong Chen, Xiaomin Dai, Lingying Ma and Lindi Jiang in Therapeutic Advances in Chronic Disease

Objective: To compare the clinical outcomes of patients with active immunoglobulin G (IgG) 4 related disease (IgG4-RD) receiving tocilizumab versus those receiving cyclophosphamide (CYC). Methods: This IgG4-RD registry study was a prospective cohort study conducted among patients with active IgG4-RD hospitalized at Zhongshan Hospital, Fudan University. Patients who were treated with tocilizumab or CYC along with glucocorticoids (GCs) were enrolled. All participants were followed up at the hospital clinic at 3 and 6 months after discharge. Primary clinical outcomes were measured via the IgG4-RD responder index (RI), complete response (CR), and partial response (PR), as well as side effects. Results: From January 2015 to June 2020, 29 patients enrolled. Fourteen and 15 patients were treated with tocilizumab and CYC, respectively. At the 6-month follow-up, disease activity parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IgG4, and IgG4-RD RI, decreased significantly in both groups. At 6 months, tocilizumab demonstrated its superiority, with 50% of patients achieving CR in the Tocilizumab group versus 20% in the CYC group. However, no statistical significance was identified ( p = 0.128). The GC dosage at 6 months was significantly lower in the tocilizumab group than in the CYC group [10 (9.4–15) mg/d versus 15 (15–15) mg/d, p = 0.025]. In the CYC group, two patients experienced lumbar vertebral compression fractures related to GCs. Other patients in both groups showed mild adverse effects. Conclusions: Tocilizumab could be a better steroid-sparing agent, with a comparable curative effect and tolerance, than CYC, in the treatment of IgG4-RD.

Patients with IgG4-related disease (IgG4-RD) suffer high relapse rates during long-term treatment, but factors that predict relapse outcomes are not well established. In the present study, we aimed to identify predictive factors for treatment resistance and disease relapse in a Chinese IgG4-RD cohort.This study enrolled 102 patients newly diagnosed with IgG4-RD. Disease prognosis was determined by evaluating disease activity and dosage of glucocorticoids. Predictive factors for refractory and relapsed disease were identified by univariate analysis and Cox regression.Among the 102 patients, 78 cases received medical treatment with regular follow-up (21 [6-111] months). During the follow-up period, 55 (70.5%) patients sustained clinical remission, and 23 (29.5%) patients suffered refractory or relapsed disease. The relapse rate of the patients with IgG4-RD was significantly higher among patients who stopped taking medicine than among those who continued treatment with glucocorticoids (GC) + immunosuppressor (IM). Serum TNF-α ≥ 13 pg/mL, sIL-2R ≥ 1010 U/mL, total cholesterol3.55 mmol/L, low-density lipoprotein2.0 mmol/L, IgG ≥ 20.2 g/L, and drug withdrawal were predictive factors for refractory and relapsed IgG4-RD. Multivariate Cox regression revealed that both sIL-2R and TNF-α were independent risk factors for refractory and relapsed disease. The combination of GC and IM treatment was an independent protective factor against refractory and relapsed IgG4-RD.High serum levels of sIL-2R and TNF-α may be informative risk factors for refractory and relapsed IgG4-RD. Our data suggest that a combination treatment of GC along with IM may be protective against refractory and relapsed IgG4-RD. Key Points • High sIL-2R and TNF-α levels are informative risk factors for refractory and relapsed IgG4-related disease. • Combination treatment of GC with IM protects against refractory and relapsed IgG4-related disease.

Background: The remarkable mechanisms of storiform fibrosis and the formation of high levels of IgG4 with a pathogenic germinal center (GC) in the inflammatory tissue of IgG4-RD remains unknown and may be responsible for the unsatisfactory therapeutic effect on IgG4-related diseases when using conventional therapy. Objectives: To investigate the mechanisms of interleukin 6 (IL-6) inducing fibroblasts to produce cytokines for pathogenic GC formation in the development of IgG4-related disease (IgG4-RD). Methods: The clinical data and laboratory examinations of 56 patients with IgG4-RD were collected. IL-6 and IL-6R expression in the serum and tissues of patients with IgG4-RD and healthy controls were detected by ELISA, immunohistochemistry, and immunofluorescence. Human aorta adventitial fibroblasts (AAFs) were cultured and stimulated with IL-6/IL-6 receptor (IL-6R). The effect of IL-6/IL-6R on AAFs was determined by Luminex assays. Results: The serum IL-6 and IL-6R levels were elevated in active IgG4-RD patients and IL-6 was positively correlated with the disease activity (e.g., erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and IgG4-RD responder index). IL-6 and IL-6R expression in the tissue lesions of IgG4-related retroperitoneal fibrosis and IgG4-related sialadenitis patients were also significantly higher than that in the normal tissues. In addition, there is a relative abundance of myofibroblasts as well as IgG4+ plasma cells in the tissues of IgG4-related retroperitoneal fibrosis. α-SMA and B cell differentiation cytokines (i.e., B cell activating factor), and α-SMA and T follicular helper (Tfh) cell differentiation cytokines (e.g., IL-7, IL-12, and IL-23) were co-expressed in the local lesions. In vitro, IL-6/IL-6R significantly promoted the production of B cell activating factor, IL-7, IL-12, and IL-23 in AAFs in a dose-dependent manner. This effect was partially blocked by JAK1, JAK2, STAT3, and Akt inhibitors, respectively. Conclusions: In vitro IL-6/IL-6R trans-signaling in fibroblasts releases Tfh and B cell differentiation factors partially via the JAK2/STAT3, JAK1/STAT3, and JAK2/Akt pathways, which may be linked to the pathogenesis of IgG4-RD. This indicated that IL-6 and fibroblasts may be responsible for GC formation and fibrosis in the development of IgG4-RD. Blocking IL-6 with JAK1/2 inhibitors or inhibiting fibroblast proliferation might be beneficial for IgG4-RD treatment.

Background: Leflunomide (LEF) has been considered as an alternative treatment for Takayasu arteritis (TA); however, data on its efficacy are still scanty. Objective: To investigate the efficacy and safety of LEF versus cyclophosphamide (CYC) for initial-onset TA. Methods: Initial-onset TA patients with active disease were enrolled in this research. Patients enrolled from 1 January 2009 to 31 December 2015 were treated with glucocorticoids and CYC, while patients enrolled from 1 January 2016 to 31 October 2018 received glucocorticoids and LEF. Treatment response including complete remission (CR), partial remission (PR), and effectiveness rate (ER) and side effects were evaluated at 6 and 12 months. Results and conclusion: In total, 92 patients were enrolled. A total of 47 patients were treated with LEF, while 45 patients were treated with CYC. The CR and ER rates were 75.55%, and 88.89% at 6 months, and 85.37% and 95.12% at 12 months in the LEF group. The CR and ER rates were 39.02% and 70.73% at 6 months, and 56.41% and 82.05% at 12 months in the CYC group. The CR rate was significantly higher in the LEF group than in the CYC group both at 6 months (75.61% versus 38.24%, p

Orbital angular momentum (OAM) beams have attracted great attention owing to their excellent performances in imaging and communication. In this paper, a dual-arm Archimedean spiral antenna (DASA) is proposed to generate multiple OAM states with positive and negative values by feeding at the inner and outer ends, respectively. The topological charge of radiated vortex waves is reconfigurable by tuning the operating frequency. Dual-mode OAM states are generated at different working frequencies (l = &plusmn, 1 at 3 GHz, l = &plusmn, 2 at 4 GHz, and l = &plusmn, 3 at 4.8 GHz). Both the simulation and measurement results demonstrate that OAM beams can be generated effectively by the DASA. In addition, a conical cavity is used to increase the gain of the proposed DASA for more than 5 dBi in comparison to the traditional cylindrical cavity. Furthermore, the qualities of the generated OAM modes by the proposed DASA have been evaluated at different operating frequencies of 3 GHz, 4 GHz, and 4.8 GHz, respectively. The OAM modes purities of l = &minus, 1, &minus, 2, &minus, 3, 1, 2, and 3 are predominate with the proportion of about 81%, 70%, 74%, 78%, 77%, and 75%, respectively. Our results demonstrate that the proposed DASA has great potentials in OAM multiplexing communication systems.

In this paper, a new kind of power generation system was built, which took solar energy as heat source of the system. All heat exchangers in the system adopted a new kind of heat exchanger type-Printed Circuit Heat Exchanger (PCHE). In order to take advantage of the abrupt property changes near the critical point of carbon dioxide, we selected recompression Brayton cycle. Then, given the operating conditions, the optimization progress was performed and the optimized parameters were obtained.

Micro-mesoporous molecular sieves are novel porous materials which are equipped with long-range parallel mesopore channels like periodic mesoporous silica (PMS) materials, and its adjacent mesopores are connected to each other through micropore walls of zeolites. Such materials can be used as highly functional adsorbents, catalyst supports and nanoreactors, because micropores and mesopores play a cooperative role as gas or fluid paths and molecular adsorption sites or reservoirs. Furthermore, the introduction of the zeolite structure provided micro-mesoporous molecular sieves significantly more acidity sites than those of PMS. In this paper, ZSM-5-MCM-41 micro-mesoporous composites are synthesized by a two-step crystallization process based on the polymerization of ZSM-5 nanocluster precursors confined to the MCM-41 structure-directing agent, and microwave radiation crystallization technology is chosen in synthesis process. In addition, the structure model of ZSM-5-MCM-41 is built by using molecular modeling technique, and then characterized by calculating the accessible solvent surface area, total pore volume, small-angle and wide-angle X-ray diffraction patterns, and toluene adsorption. The calculated results are proved and compared with corresponding experiment results, such as N 2 adsorption–desorption isotherms, X-ray power diffraction patterns, and toluene adsorption.

Dynamic performance targets were designed for dual-motor-driven vehicle, and a driving motor power calculation model was established based on the vehicle dynamics, and the formulas of electric vehicles dynamic performance parameters such as the transmission gear ratio, the vehicle maximum speed and acceleration time were given out. The performance was calculated by the Cruise software, and the simulation results show that, the design requirements of the vehicle dynamic performance were met by the system dynamic performance.

As the main structure-directing template, P123 performs a key role during the formation of the bimodal pore system of the micro–mesoporous silica SBA-15. In this paper, the method of mesoscopic dynamics (MesoDyn) has been applied to simulate the aggregation behaviour of the triblock copolymer P123 (PEO 20 PPO 70 PEO 20 ), and to further explore the structure-formation mechanism and analyze the feasibility of accurately adjusting the pore size of SBA-15. In particular, the effect of the synthesis temperature on the P123 micelle size in the SBA-15 synthesis process has been investigated in detail due to its importance in adjusting the pore size of SBA-15. In addition, in order to validate the simulation results, a series of SBA-15 samples were synthesized at temperatures within the range 293–328 K. The simulation results show that uniform spherical micelles of P123, composed of hydrophilic PEO coronas and hydrophobic PPO cores, can be formed in aqueous solutions. This provides a perfect explanation of the experimental findings of previous work. Moreover, it has also been found that the P123 micelle gradually expands as the temperature increases, which leads directly to an increase in the mesopore diameter of SBA-15. The relevant experimental results reported in this paper demonstrate this conclusion. Overall, the mesoscopic simulation method has been shown to be a valuable tool for exploring structure fabrication and for providing an accurate guide for adjusting the pore size of SBA-15, as well as being a strong complement and extension to the experimental approach.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01 AR070148]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54 AR057319, U01 AR51874 04]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; Office of Rare Diseases Research of the National Center for Advancing Translational Sciences; Imperial College, National Institute for Health Research, Biomedical Research Centre; Wellcome TrustWellcome TrustEuropean Commission [WT107881]; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_UU_00002/4], This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health grant R01 AR070148 to A.H.S. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences. J.C.M., A.P.K., and R.M.M. acknowledge support from the Imperial College, National Institute for Health Research, Biomedical Research Centre. C.W. and G.R. acknowledge support from The Wellcome Trust (WT107881) and the Medical Research Council (MC_UU_00002/4). This work was supported by the use of study data downloaded from the dbGaP website, under dbGaP: phs000272.v1.p1, phs000431.v2.p1, phs000583.v1.p1, and phs000444.v1.p1.