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Background. Takayasu arteritis is a rare disease characterized by inflammation in the aorta and its branches. Some patients were discovered to suffer the aggravated vascular damage (AVD), monitored by imaging techniques, even with the anti-inflammation treatment. But the overall characteristics and prognostic factors of AVD remained unclear yet. Methods. From the living East China Takayasu arteritis cohort, patients who underwent at least two magnetic resonance angiography (MRA) examinations at Zhongshan Hospital from April 2009 to April 2019 were enrolled as the derivation cohort to describe the characteristics of AVD and explore the prognostic factors of AVD in MRA. An independent group of patients from May 2019 to July 2020 comprising the validation cohort were used to validate the nomogram formed by these prognostic factors. Results. Among 235 enrolled patients, 69 patients (29.4%) suffered AVD with the median follow-up of 14 months. The limb arteries and vascular stenosis were the most common vascular location and manifestation of AVD respectively. Patients with AVD were younger, had higher complement 4 levels at baseline, and lower disease remission rate at 6 months. Cox regression analysis revealed that younger age (HR: 0.25-0.42, 95%CI: 0.09-0.91), higher CRP levels (HR = 2.57, 95%CI: 1.51–4.36) at baseline, and lower remission rate at 6 months (HR = 0.36, 95%CI: 0.21–0.64) were significant predictors. In the validation cohort of 65 patients, 19 cases had AVD. The predictive nomogram based on these factors achieved C-indices of 0.745 and 0.641 in the derivation and validation cohort respectively.Conclusions. Totally, 29.4% of patients suffered AVD, which manifested as vascular stenosis in limb arteries mainly. Younger age, higher CRP at baseline, and lower disease remission rate at 6 months were prognostic factors for AVD.

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 hypertensive TAK population. Methods This current research was based on a prospectively on-going observational cohort-the East China Takayasu Arteritis (ECTA) cohort, centered in Zhongshan Hospital, Fudan University. Totally, 204 hypertensive TAK patients 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, and 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 three imaging clusters. In all, 187 patients were followed-up for a median of 46 (9-102) months; 127 (67.9%) cases did not experience any events, while 72 events were observed in 60 patients. 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, patients had controlled blood pressure and Cluster 1 phenotype was set as reference, better EFS was observed in patients with controlled blood pressure and Cluster 2 phenotype (HR = 2.21, 95%CI 1.47–4.32), while those had uncontrolled blood pressure and Cluster 1 phenotype (HR = 0.64, 95%CI: 0.52–0.89) and those had uncontrolled blood pressure and Cluster 3 phenotype (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 hypertensive TAK.

Background: Melanoma has dramatically increased during last 30 years with low five-year survival and prognosis rate.Methods: Melanoma cells (A375 and G361) were chosen as in vitro model. The interference and overexpression of PCDH9 were infected by lentivirus. The effects of PCDH9 on melanoma cells were assessed in terms of alteration of PCDH9 such as cell viability, apoptosis, cell cycle and wound-healing assay. Moreover, expressions of PCDH9 with other genes (MMP2, MMP9, Pyk2 Cyclin D1, RAC1 and FAK) were also assessed by PCR and western blotting, immunohistochemical analysis. The protein complex immunoprecipitation was operated for protein-protein interaction (PPI) of PCDH9. Originlab 2020 was used for statistical analysis.Results: Melanoma cells treated with PCDH9 showed influence melanoma as similar function as Hace1 that regulate RAC1/ROS-dependent NADPH oxidase complexes through targeting complex-bound RAC1 with the help of Pyk2, while RAC1 directly influence RAC1/ROS-NADPH-oxidase complex to induce metalloproteinases (MMPs), that are involved in cell migration and proliferation. Moreover, PCDH9 could influence the expressions of MMP2, MMP9, Pyk2, Cyclin D1 and RAC1, except FAK, decreased cell viability, cell migration and increased apoptosis, but did not exert significant effects on cell cycle. Besides, the immunohistochemical results exhibited lower PCDH9 expression in malignant melanoma samples than benign naevus tissue or/and normal skin, and PCDH9 was expressed in the cytoplasm rather than nuclei. The results of immunoprecipitation demonstrated that PCDH9 bind with RAC1 and Pyk2, suggesting the regulation of PCDH9 to melanoma progression. Conclusion: Our results suggest that PCDH9 and RAC1 could predict for potential biomarkers prognosis of malignant melanoma, interestingly, with Pyk2’s assistance like a bridge PCDH9 can modulate melanoma progression by interacting with RAC1.

Background. Takayasu arteritis (TA) is a rare disease, lacking convenient and feasible biomarkers to identify disease activity. We aimed to evaluate the value of complements in distinguishing active TA. Methods. Consecutive patients were enrolled from the prospective East China TA cohort from April 2008 to June 2019. Patients were divided into two groups according to their baseline Kerr score. The value of complements and other biomarkers in identifying disease activity were analysed. An independent group of patients from July 2019 to December 2019 were employed to validate the results.Results. Of the enrolled 519 patients, 406 (72.2%) cases were identified as active disease. Higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), and complement 3 (C3) levels were observed in the active group. Elevated C3 (≥1.085 g/L) had a high value to identify active TA with a sensitivity of 69.9%, specificity of 66.7% and AUC of 0.715. Combining the CRP (≥10.65 g/L; sensitivity, 50.7%; specificity, 82.4%) and C3, the sensitivity could be improved to 85.1% in parallel test and the specificity could be improved to 94.1% in serial test. Validation was further performed to confirm the value of C3 for disease activity assessment. The accuracy of the parallel test of CRP and C3 in external validation with independent 53 TA cases was 72.73% with the AUC of 0.721. Conclusion. Elevated C3 could effectively monitor the disease activity of TA, and C3 combining with CRP could further improve the disease activity evaluation.

Background Takayasu’s arteritis (TAK) is a chronic inflammatory disease characterized by macrophage infiltration. During the active stage, aorta adventitial fibroblasts (AAFs) proliferate excessively and produce numerous pro-inflammatory factors in the adventitia, the primary target of TAK therapy. Although the monocyte chemokine, CCL2, may contribute to macrophage infiltration in TAK arteries, whether there is an associated relationship with HSP65 remains unknown. Moreover, there are no reports of the activation of AAFs to produce inflammatory factors involvement in TAK pathogenesis. TAK treatment is associated with several challenges and contradictions. Curcumin is a traditional Chinese medicine with anti-inflammatory effects; however, its effectiveness for TAK and the underlying mechanism remains unclear. Methods We first verified high HSP65 expression in the aortic adventitia of TAK patients by IHC. mRNA-seq was used to profile differentially expressed genes (DEGs) between AAFs stimulated by HSP65 with or without pretreatment with curcumin, and untreated AAFs. The key chemokine, CCL2, screened by mRNA-seq was detected in the adventitia of the TAK aorta, and its correlation with HSP65 expression was analyzed by double-labelled immunofluorescence. We subsequently explored how HSP65 affected the production of inflammatory factors by AAFs at a cellular level and the related signaling pathway. We explored whether curcumin could hinder this process and verified the effect of curcumin on the level of serum CCL2 in patients with TAK. Results HSP65 was highly expressed in the adventitia of TAK arteries. The DEG analysis showed a key role of CCL2. The expression of CCL2 in the adventitia of TAK arteries was significantly higher than that of healthy subjects, and was correlated with HSP65. HSP65 facilitated the production of CCL2, IL-6, and IL-1β by AAFs via activation of the TLR4-JAK2/AKT/STAT3 pathway, among which the change in CCL2 was the greatest. Curcumin treatment reversed HSP65-induced CCL2 upregulation in vitro, which was more obvious than that of MTX and tofacitinib. Finally, curcumin significantly downregulated the level of serum CCL2 in TAK patients. Conclusion HSP65 initiates and promotes TAK inflammation by upregulating CCL2 in AAFs through the JAK2/AKT/STAT3 pathway, whereas curcumin could reverse this process and slow the initiation and development of TAK.

Background: Takayasu arteritis (TA) is a large-vessel vasculitis that can involve pulmonary arteries (PAs). We studied multiple clinical characteristics related to pulmonary artery involvement (PAI) in TA patients. Methods: We enrolled 216 patients with TA from a large prospective cohort. PAI was assessed in each patient based on data from magnetic resonance angiography/computed tomography angiography. Pulmonary hypertension, cardiac function, and pulmonary parenchymal lesions were evaluated further in patients with PAI based on echocardiography, New York Heart Association Functional Classification and pulmonary computed tomography, respectively. These abnormalities related to PAI were followed up to evaluate treatment effects. Results: PAI was detected in 56/216 (25.93%) patients, which involved the pulmonary trunk, main PAs and small vessels in the lungs. Among patients with PAI, 28 (50%) patients were accompanied by pulmonary hypertension, which was graded as ‘severe’ in 9 (16.07%), ‘moderate’ in 10 (17.86%) and mild in 9 (16.07%). Twenty-six patients (46.43%) patients showed advanced NYHA function (III: 20, 35.71%; IV: 6, 10.71%). Furthermore, 21 (37.50%) patients presented with abnormal pulmonary parenchymal lesions in the area corresponding to PAI (e.g., the mosaic sign, infarction, bronchiectasis). During follow-up, two patients died due to heart failure and pulmonary thrombosis. In the remaining patients, the abnormalities mentioned above improved partially after routine treatment. Conclusions: PAI is common in TA patients. PAI can cause pulmonary hypertension, cardiac insufficiency and pulmonary parenchymal lesions, which worsen patients’ prognosis.

Background Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of immune system, which is recently concerned as a significant factor for increased risk of various morbidities. Nevertheless, there are few dates explicating the relevancy of T cell senescence to mortality. In this study, we prospectively studied the predictive value of T cell senescence for mortality in hemodialysis patients. Methods Patients who had been on hemodialysis treatment for at least 6 months were enrolled. T cell senescence determined by differentiation status was evaluated by flow cytometry. Survival outcomes were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to evaluate the prognostic impact of T cell premature aging and other clinical factors on all-cause mortality. Results A total of 466 patients (277 man and 169 women) were enrolled in this study. Decreased number of naïve T cell, as the most prominent feature of T cell senescence, did not change in parallel with age in these patients. Decreased absolute count of T cell, naïve T cell, CD4+ naïve T cell were independently associated with all-cause mortality. Decreased percentage of T cell and increased percentage of CD8+central-memory T cell were also independently associated with all-cause mortality. After including all the T cell parameters in one regression model, only decreased count of naïve T cell was significantly associated with increased mortality in these patients. Conclusions Aging-associated T cell changes are aggravated in ESRD patients. For the first time, our study demonstrates that naïve T cell depletion is a strong predictor of all-cause mortality in HD patients.

Background: Takayasu arteritis (TA) is a large-vessel vasculitis that can involve pulmonary arteries (PAs). We studied multiple clinical characteristics related to pulmonary artery involvement (PAI) in TA patients.Methods: We enrolled 216 patients with TA from a large prospective cohort. PAI was assessed in each patient based on data from magnetic resonance angiography/computed tomography angiography. Pulmonary hypertension, cardiac function, and pulmonary parenchymal abnormalities were evaluated further in patients with PAI based on echocardiography, New York Heart Association Functional Classification and pulmonary computed tomography, respectively. These abnormalities related to PAI were followed up to evaluate treatment effects.Results: PAI was detected in 56/216 (25.93%) patients, which involved the pulmonary trunk, main PAs and small vessels in the lungs. Among patients with PAI, 28 (50%) patients were accompanied by pulmonary hypertension, which was graded as ‘severe’ in 9 (16.07%), ‘moderate’ in 10 (17.86%) and mild in 9 (16.07%). Forty (71.43%) patients had cardiac insufficiency (IV: 6, 10.71%; III: 20, 35.71%; II: 14, 25.00%). Furthermore, 21 (37.50%) patients presented with abnormal parenchymal features in the area corresponding to PAI (e.g., the mosaic sign, infarction, bronchiectasis). During follow-up, two patients died due to abrupt pulmonary thrombosis. In the remaining patients, the abnormalities mentioned above improved partially after routine treatment.Conclusions: PAI is very common in TA patients. PAI can cause pulmonary hypertension, cardiac insufficiency and pulmonary parenchymal lesions, which worsen the prognosis.

Objective: The aim of this study was to describe the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in eastern China using data from a hospital-based study. And looking for indicators that can predict disease activity. Methods: We retrospectively studied patients with newly diagnosed AAV evaluated from January 1, 2009, to December 31, 2018 . In total, 219 patients diagnosed were classified according to the American College of Rheumatology classification criteria and/or revised Chapel Hill 2012 definitions, and their clinical and serological features were evaluated. The association of laboratory data with disease activity was assessed via regression models. Results: Of 219 incident cases of AAV, 37/219 (16.9%) had granulomatosis with polyangiitis (GPA), 172/219 (78.5%) were microscopic polyangiitis (MPA), and 10/219 (4.6%) had eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis of patients with GPA were 51.5 years (male/female, 18/19), MPA were 61. 7 years (male/female, 84/88), and EGPA were 49.8 years ( male/female, 7/3), respectively. Patients with MPA were significantly older than GPA and EGPA at diagnosis ( p 0.215 g/L) were proved to be independent risk factors for active disease. Further research showed that C4 had higher sensitivity (70.0%) and specificity (83.4%) than the other three indicators. Conclusion: MPO-ANCA-positive MPA is the most common form of AAV in Chinese patients. Serum C4 concentrations at diagnosis might be a useful biomarker of disease activity in AAV.