Publications by authors named "Junyan Qian"

21 Publications

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The LPS induced pyroptosis exacerbates BMPR2 signaling deficiency to potentiate SLE-PAH.

FASEB J 2021 Dec;35(12):e22044

Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Pulmonary arterial hypertension (PAH) is a common and fatal complication of systemic lupus erythematosus (SLE). Whether the BMP receptor deficiency found in the genetic form of PAH is also involved in SLE-PAH patients remains to be identified. In this study, we employed patient-derived samples from SLE-associated PAH (SLE-PAH) and established comparable mouse models to clarify the role of BMP signaling in the pathobiology of SLE-PAH. Firstly, serum levels of LPS and autoantibodies (auto-Abs) directed at BMP receptors were significantly increased in patients with SLE-PAH compared with control subjects, measured by ELISA. Mass cytometry was applied to compare peripheral blood leukocyte phenotype in patients prior to and after treatment with steroids, which demonstrated inflammatory cells alteration in SLE-PAH. Furthermore, BMPR2 signaling and pyroptotic factors were examined in human pulmonary arterial endothelial cells (PAECs) in response to LPS stimulation. Interleukin-8 (IL-8) and E-selectin (SELE) expressions were up-regulated in autologous BMPR2 endothelial cells and siBMPR2-interfered PAECs. A SLE-PH model was established in mice induced with pristane and hypoxia. Moreover, the combination of endothelial specific BMPR2 knockout in SLE mice exacerbated pulmonary hypertension. Pyroptotic factors including gasdermin D (GSDMD) were elevated in the lungs of SLE-PH mice, and the pyroptotic effects of serum samples isolated from SLE-PAH patients on PAECs were analyzed. BMPR2 signaling upregulator (BUR1) showed anti-pyroptotic effects in SLE-PH mice and PAECs. Our results implied that deficiencies of BMPR2 signaling and proinflammatory factors together contribute to the development of PAH in SLE.
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http://dx.doi.org/10.1096/fj.202100851RRDOI Listing
December 2021

Ten-year survival analysis of patients with primary Sjögren's syndrome in China: a national prospective cohort study.

Ther Adv Musculoskelet Dis 2021 23;13:1759720X211020179. Epub 2021 Jun 23.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100730, China.

Aims: To investigate the long-term survival of patients with primary Sjögren's syndrome (pSS) in China.

Methods: Patients with pSS who fulfilled the 2002 American-European Consensus Group classification criteria were prospectively enrolled from 2004 to 2011. Their baseline clinical, laboratory, and therapeutic data were collected. The primary endpoint was all-cause death by January 2018. The standard mortality ratio (SMR) was calculated by comparing with age-matched and sex-matched mortality data of the general population. Kaplan-Meier curves were obtained by time-to-event analysis. Univariate and multivariate Cox hazards regression analyses were performed to identify risk factors for mortality.

Results: A total of 1054 patients were enrolled and 834 patients were followed up for a median of 94.8 months, with 48 confirmed deaths. The total SMR was 3.63 [95% confidence interval (CI) 2.60-4.66]. The 3-, 5-, and 10-year survival rates were 98.4%, 97.5%, and 92.9%, respectively. Infection, malignancy, and respiratory failure were the top three causes of mortality. We identified male sex [hazard ratio (HR) = 3.00, 95% CI 1.23-7.31], age at diagnosis ⩾50 years of age (HR = 7.69, 95% CI 3.01-19.62), thrombocytopenia (HR = 1.93, 95% CI 1.01-3.72), and interstitial lung disease (HR = 5.96, 95% CI 2.24-15.82) as the independent prognostic factors of death.

Conclusions: The mortality rates of Chinese patients with pSS are higher than those of the general population. Male patients of elder age at diagnosis complicated with thrombocytopenia and interstitial lung disease might be suggestive for poorer survival and require closer follow up.
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http://dx.doi.org/10.1177/1759720X211020179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237224PMC
June 2021

Validation of the REVEAL Prognostic Models in Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension.

Front Med (Lausanne) 2021 4;8:618486. Epub 2021 Mar 4.

Department of Epidemiology and Bio-Statistics, Institute of Basic Medical Sciences, China Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

No previous studies have investigated the predictive performance of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) prognostic equation and simplified risk score calculator in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). We aimed to validate these prediction tools in an external cohort of patients with SLE-PAH. In this study, the validation cohort consisted of patients with SLE-PAH registered in a prospective, multicenter, nationwide database between November 2006 and May2016. The follow-up of patients was censored at 1 year. Discrimination, calibration, model fit, and risk stratification of the REVEAL prognostic equation and simplified risk score calculator were validated. As a result, a total of 306 patients with SLE-PAH were included. The 1-year overall survival rate was 91.5%. The C-index of the prognostic equation was 0.736, demonstrating reasonably good discrimination, and it was greater than that for the simplified risk score calculator (0.710). The overall calibration slope was 0.83, and the Brier score was 0.079. The risk of renal insufficiency and World Health Organization Functional Class III (WHO FC III) were underestimated, and the risk assigned to a heart rate >92 bpm in the REVEAL prognostic models was not observed in our validation cohort. Both model discrimination and calibration were poor in the very high-risk group. In conclusion, the REVEAL models exhibit good discriminatory ability when predicting 1-year overall survival in patients with SLE-PAH. Findings from both models should be interpreted with caution in cases of renal insufficiency, WHO FC III, and heart rate >92 bpm.
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http://dx.doi.org/10.3389/fmed.2021.618486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969505PMC
March 2021

Chinese SLE Treatment and Research Group Registry (CSTAR) XIII: prevalence and risk factors for chronic scarring alopecia in patients with systemic lupus erythematosus.

Arthritis Res Ther 2021 01 11;23(1):20. Epub 2021 Jan 11.

Department of Rheumatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China.

Background: Scarring alopecia in systemic lupus erythematosus (SLE) patients caused reduced life quality and prolonged disease course. This case-control study aims to survey the prevalence of scarring alopecia during the disease course of SLE and evaluate the risk factors for scarring alopecia in Chinese SLE patients.

Methods: SLE patients in Chinese SLE treatment and Research group (CSTAR) were recruited. Scarring alopecia was defined according to SLICC/ACR-DI which was collected during follow-up visits or via self-reported questionnaires. We collected demographic characteristics, common comorbidities, autoantibody profiles, disease activity status, major organ involvements, and treatment strategies of these patients at registry. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for scarring alopecia.

Results: We recruited 4792 SLE patients, and 374 (7.80%) patients had scarring alopecia. Mucocutaneous lesions (OR 2.062, p < 0.001), high SLICC/ACR-DI (OR 1.409, p < 0.001), and positive anti-Sm (OR 1.374, p = 0.029) were risk factors for scarring alopecia, while renal (OR 0.714, p = 0.028) and cardio-respiratory involvements (OR 0.347, p = 0.044), and immunosuppressant treatment (OR 0.675, p < 0.001) were significantly negative associated with it.

Conclusions: The prevalence of scarring alopecia in SLE patients is 7.80%. Active treatment strategies should be adopted to prevent scarring alopecia occurring.
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http://dx.doi.org/10.1186/s13075-020-02407-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802218PMC
January 2021

Clinical efficacy and safety of sirolimus in systemic lupus erythematosus: a real-world study and meta-analysis.

Ther Adv Musculoskelet Dis 2020 14;12:1759720X20953336. Epub 2020 Sep 14.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan, Beijing 100730, China.

Objective: To provide real-world data and summarize current clinical evidence on the efficacy and safety of sirolimus in active systemic lupus erythematosus (SLE) patients.

Methods: This was a prospective real-world clinical study. Included SLE patients should have Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ⩾ 2. They were treated with sirolimus and followed up regularly. The SLEDAI-2K, Physician Global Assessment (PGA), serological activity indices, and remission of organ manifestations were evaluated. We also performed a meta-analysis to integrate current evidence of sirolimus in SLE.

Results: A total of 49 patients were included in the final analysis. After treatment, the SLEDAI-2K (6.2 ± 3.1 4.0 ± 3.4,  = 0.001) decreased significantly, and the prednisone dosage was tapered successfully (9.9 ± 8.8 mg/day 5.9 ± 4.0 mg/day,  = 0.002). Serological activity indices also improved [complement 3 (C3): 0.690 ± 0.209 g/l 0.884 ± 0.219 g/l,  < 0.001; complement 4: 0.105 ± 0.059 g/l 0.141 ± 0.069 g/l,  < 0.001; anti-dsDNA antibody, 200 ± 178 IU/ml 156 ± 163 IU/ml,  = 0.022]. The remission proportions of arthritis, skin rash, and thrombocytopenia were 100%, 88.8%, and 46.2%, respectively. A total of 41.2% of lupus nephritis (LN) patients achieved renal remission, but the average 24-h urine protein level was not significantly changed. Meta-analysis enrolled five studies with 149 patients included, and revealed similar results regarding the changes of SLEDAI-2K [-3.5 (-5.0, -2.1)], C3 [0.224 (0.136, 0.311) g/l] and daily dosage of prednisone [-12.7 (-19.9, -5.6) mg/day].

Conclusion: Sirolimus might be effective and tolerated in SLE. The role of sirolimus in LN requires further study.
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http://dx.doi.org/10.1177/1759720X20953336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493251PMC
September 2020

Pulmonary arterial hypertension associated with primary Sjögren's syndrome: a multicentre cohort study from China.

Eur Respir J 2020 11 19;56(5). Epub 2020 Nov 19.

Dept of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China

Objectives: Primary Sjögren's syndrome (pSS) is an important cause of pulmonary arterial hypertension (PAH), which remains insufficiently studied and needs attention. This study aimed to investigate the clinical characteristics, risk factors, prognosis and risk assessment of pSS-PAH.

Methods: We established a multicentre cohort of pSS-PAH diagnosed by right heart catheterisation. The case-control study was conducted with pSS-non-PAH patients as a control group to identify the risk factors for PAH. In the cohort study, survival was calculated, and risk assessment was performed at both baseline and follow-up visits.

Results: In total, 103 patients with pSS-PAH were enrolled, with 526 pSS-non-PAH patients as controls. The presence of anti-SSB (p<0.001, OR 4.095) and anti-U1RNP antibodies (p<0.001, OR 29.518), the age of pSS onset (p<0.001, OR 0.651) and the positivity of corneal staining (p=0.003, OR 0.409) were identified as independent risk factors for PAH. The 1-, 3- and 5-year survival rates were 94.0%, 88.8% and 79.0%, respectively. Cardiac index (p=0.010, hazard ratio (HR) 0.161), pulmonary vascular resistance (p=0.016, HR 1.105) and Sjögren's syndrome disease damage index (p=0.006, HR 1.570) were identified as potential predictors of death in pSS-PAH. Long-term outcomes were improved in patients in the low-risk category at baseline (p=0.002) and follow-up (p<0.0001).

Conclusion: The routine screening of PAH is suggested in pSS patients with early onset and positivity for anti-SSB or anti-U1RNP antibodies. Patient prognosis might be improved by improving reserved cardiopulmonary function, by achieving a damage-free state and especially by achieving low-risk category, which supports the treat-to-target strategy for pSS-PAH.
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http://dx.doi.org/10.1183/13993003.02157-2019DOI Listing
November 2020

IoT-RECSM-Resource-Constrained Smart Service Migration Framework for IoT Edge Computing Environment.

Sensors (Basel) 2020 Apr 17;20(8). Epub 2020 Apr 17.

Department of Eletrical Engineering, Universidad de Chile, Santiago 1025000, Chile.

The edge-based computing paradigm (ECP) becomes one of the most innovative modes of processing distributed Interneit of Things (IoT) sensor data. However, the edge nodes in ECP are usually resource-constrained. When more services are executed on an edge node, the resources required by these services may exceed the edge node's, so as to fail to maintain the normal running of the edge node. In order to solve this problem, this paper proposes a resource-constrained smart service migration framework for edge computing environment in IoT (IoT-RECSM) and a dynamic edge service migration algorithm. Based on this algorithm, the framework can dynamically migrate services of resource-critical edge nodes to resource-rich nodes. In the framework, four abstract models are presented to quantificationally evaluate the resource usage of edge nodes and the resource consumption of edge service in real-time. Finally, an edge smart services migration prototype system is implemented to simulate the edge service migration in IoT environment. Based on the system, an IoT case including 10 edge nodes is simulated to evaluate the proposed approach. According to the experiment results, service migration among edge nodes not only maintains the stability of service execution on edge nodes, but also reduces the sensor data traffic between edge nodes and cloud center.
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http://dx.doi.org/10.3390/s20082294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219074PMC
April 2020

Pulmonary arterial hypertension in systemic lupus erythematosus based on a CSTAR-PAH study: Baseline characteristics and risk factors.

Int J Rheum Dis 2019 May 11;22(5):921-928. Epub 2019 Feb 11.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Aim: Pulmonary arterial hypertension (PAH) is a complex and devastating complication of systemic lupus erythematosus (SLE). We sought to describe the baseline characteristics of right heart catheterization (RHC)-confirmed SLE-associated PAH and identify risk factors for PAH in SLE patients.

Methods: A multicenter, cross-sectional study was conducted using the Chinese SLE Treatment and Research group (CSTAR) registry. Baseline data for patients with SLE-associated PAH and SLE patients without PAH were collected and compared. Risk factors for PAH among patients with SLE were identified.

Results: A total of 292 patients with SLE-associated PAH were enrolled. RHC was used to reveal hemodynamic features, including mean pulmonary arterial pressure (46.2 ± 12.0 mm Hg), pulmonary arterial wedge pressure (7.84 ± 3.92 mm Hg), pulmonary vascular resistance (10.86 ± 5.57 Wood units), and cardiac index (2.77 ± 0.91 L/min × m ). A multivariate logistic regression analysis showed that serositis (odds ratio [OR] = 5.524, 95% CI 3.605-8.465, P < 0.001), anti-ribonucleoprotein (RNP) antibody positivity (OR = 13.332, 95% CI 9.500-18.710, P < 0.001), and diffusion capacity of carbon monoxide in the lung (DLCO)/%Pred <70% (OR = 10.018, 95% CI 6.619-15.162, P < 0.001) were independent predictors of PAH. We recommend using transthoracic echocardiography (TTE) to perform early screening of SLE patients who have serositis, anti-RNP antibody positivity, or DLCO/%Pred <70%. RHC is suggested for patients suspected of having PAH. Once a diagnosis of SLE-PAH is confirmed, evaluation and treatment should immediately begin.

Conclusion: Overall, we recommend performing early screening using TTE in SLE patients with serositis, anti-RNP antibodies, or a DLCO/%Pred <70%, even for patients in a relatively stable condition according to SLE disease activity index.
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http://dx.doi.org/10.1111/1756-185X.13478DOI Listing
May 2019

Long-term prognosis of patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

Eur Respir J 2019 02 14;53(2). Epub 2019 Feb 14.

Dept of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

This study aimed to identify the long-term clinical outcomes and prognostic factors of patients with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) confirmed by right heart catheterisation.A multicentre prospective cohort of SLE-associated PAH was established. Baseline and follow-up records were collected. The primary end-point was death. The secondary exploratory end-point was treatment goal achievement (TGA), defined as an integrated outcome.In total, 310 patients were enrolled from 14 PAH centres. The 1-, 3- and 5-year survival rates were 92.1%, 84.8% and 72.9%, respectively. The 1-, 3- and 5-year TGA rates were 31.5%, 53.6% and 62.7%, respectively. Baseline serositis, 6-min walking distance >380 m and cardiac index ≥2.5 L·min·m were identified as independent prognostic factors of TGA. Patients with baseline serositis were more likely to reach TGA after intensive immunosuppressive therapy. TGA was identified as a positive predictor of survival in patients with SLE-associated PAH.TGA was associated with long-term survival, which supports the treat-to-target strategy in SLE-associated PAH. Baseline heart function predicted both survival and treatment goal achievement in patients with SLE-associated PAH. Patients with serositis at baseline tended to benefit from intensive immunosuppressive therapy and have a better clinical outcome.
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http://dx.doi.org/10.1183/13993003.00081-2018DOI Listing
February 2019

Cysteine-rich protein 61 as a novel biomarker in systemic lupus erythematosus-associated pulmonary arterial hypertension.

Clin Exp Rheumatol 2019 Jul-Aug;37(4):623-632. Epub 2018 Dec 20.

Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, China.

Objectives: This study aimed to evaluate the level of plasma Cysteine rich 61 (Cyr61) in systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) patients, and to explore the diagnostic and prognostic value of Cyr61 in SLE-PAH.

Methods: Plasma samples were obtained from 54 patients with definite SLE-PAH, 52 SLE-non-PAH patients and 54 healthy controls. Enzyme-linked immunosorbent assay was used to measure plasma Cyr61 concentration, and immunohistochemistry assay was adopted to identify Cyr61 protein expression in lung tissues of monocrotaline (MCT) induced PAH rats at different stages.

Results: Plasma Cyr61 concentration in SLE-PAH patients was significantly higher than matched SLE-non-PAH patients and healthy controls. The optimal cut-off value of Cyr61 in predicting the presence of PAH in entire SLE was 140.7 pg/ml. Further multivariate logistic regression analysis revealed that Cyr61 level≥140.7 pg/ml was an independent risk factor for developing PAH in SLE patients. Kaplan-Meier analysis indicated that SLE-PAH patients with Cyr61 level ≥140.7 pg/ml had better survival than those with lower Cyr61 level (p=0.001 by Log-Rank test), and this was also confirmed by multivariate Cox regression analysis. In addition, Cyr61 protein expression was significantly higher in lung tissue of MCT induced PAH rats compared to control rats, and the expression was more significant in early-mid stage of PAH development than the late stage.

Conclusions: Plasma Cyr61 level was significantly higher in SLE-PAH patients. Elevated circulating Cyr61 is a useful biomarker for identifying PAH in SLE, and it may serve as a promising indicator of prognosis in SLE-PAH.
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July 2019

Inflammation in SLE-PAH: good news or not?

Ann Rheum Dis 2019 12 14;78(12):e135. Epub 2018 Nov 14.

Department of Rheumatology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China

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http://dx.doi.org/10.1136/annrheumdis-2018-214605DOI Listing
December 2019

Red blood cell distribution width as a potential predictor of survival of pulmonary arterial hypertension associated with primary Sjogren's syndrome: a retrospective cohort study.

Clin Rheumatol 2019 Feb 14;38(2):477-485. Epub 2018 Sep 14.

Department of Rheumatology, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Pulmonary arterial hypertension (PAH) is a severe complication and leading cause of mortality in patients with primary Sjogren's syndrome (pSS). This study was to investigate the overall survival rates and the utility of red blood cell distribution width (RDW) as a potential prognostic factor of pSS-PAH. This cohort study retrospectively enrolled 55 patients with pSS-PAH who were followed up at the Department of Rheumatology of Peking Union Medical College Hospital (PUMCH) between August 2007 and May 2017. The patients were stratified according to the level of RDW (≤ 15.0 and > 15.0%). Baseline demographics, laboratory results, pulmonary function conditions, hemodynamic assessments, and treatment regimens were analyzed. Cox proportional hazards regression analysis was used to identify whether RDW level is a factor related to adverse outcome. A total of 55 patients were recruited, with an average age of 38.9 ± 9.3 years. Fifty-four were female (98.2%), and the average duration at the time of PAH diagnosis was 25.5 ± 33.2 months. Higher RDW levels were found in patients who deceased in follow-up (13.8 ± 2.6 vs 16.5 ± 1.6%, p = 0.003) and with higher NYHA classes (13.8 ± 1.8 vs 16.5 ± 2.9%, p < 0.001). Patients with RDW > 15% had a significantly worse overall survival than patients with RDW ≤ 15% (3-year survival rate 59.5 vs. 88.7% log-rank p = 0.015). Cox regression analysis identified RDW > 15% as a prognostic factor for adverse outcome (HR 1.786, 95% CI 1.137-2.803, p = 0.012). RDW can serve as a potential negative prognostic factor of pSS-PAH.
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http://dx.doi.org/10.1007/s10067-018-4281-1DOI Listing
February 2019

Is it possible to apply the treat-to-target strategy in primary Sjögren's syndrome-associated pulmonary arterial hypertension?

Clin Rheumatol 2018 Nov 24;37(11):2989-2998. Epub 2018 Jul 24.

Department of Rheumatology, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing, 100730, China.

The treat-to-target (T2T) strategy improved long-term survival of patients with pulmonary arterial hypertension (PAH). Little was known about applying the T2T strategy in primary Sjogren's syndrome-associated PAH (pSS-PAH). We investigated how to identify patients who are more likely to reach the treatment goals in a cohort of pSS-PAH. In this way, we explored the possibility of implementing T2T in pSS-PAH. Data were retrospectively collected from patients visiting our center between 2007 and 2017. PAH was confirmed by right heart catheterization (RHC). Patients were treated following the T2T strategy. PAH treatment goals were defined by the 5th World Symposium on Pulmonary Hypertension. The primary end point was reaching the PAH treatment goals. Of the 62 patients enrolled, 98.4% were female, with a mean age of 38.9 ± 9.1 years at the diagnostic RHC. The median disease duration of pSS was 46 months (0-365), while the median disease duration of PAH was 12 months (0-149). Following the T2T strategy, 32 (50%) patients achieved the treatment goals. The 1-, 3-, and 5- year cumulative rates of reaching the goals were 40.6, 67.4, and 73.9%, respectively. Predictive factors included using immunosuppressants (HR 4.715, 95% CI 1.101-20.192, p = 0.037) and right ventricular anterior-posterior diameter (RV-APD) > 30 mm at baseline (HR 0.426, 95% CI 0.188-0.968, p = 0.042). The results provide strong evidence that patients who received immunosuppressants are more likely to reach the treatment goals. In contrast, impaired RV structure correlates to worse treatment response. The T2T strategy is effective in pSS-PAH.
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http://dx.doi.org/10.1007/s10067-018-4184-1DOI Listing
November 2018

Path-oriented test cases generation based adaptive genetic algorithm.

PLoS One 2017 14;12(11):e0187471. Epub 2017 Nov 14.

Department of Information Technology, Zhejiang Sci-Tech University, Hangzhou, China.

The automatic generation of test cases oriented paths in an effective manner is a challenging problem for structural testing of software. The use of search-based optimization methods, such as genetic algorithms (GAs), has been proposed to handle this problem. This paper proposes an improved adaptive genetic algorithm (IAGA) for test cases generation by maintaining population diversity. It uses adaptive crossover rate and mutation rate in dynamic adjustment according to the differences between individual similarity and fitness values, which enhances the exploitation of searching global optimum. This novel approach is experimented and tested on a benchmark and six industrial programs. The experimental results confirm that the proposed method is efficient in generating test cases for path coverage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187471PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685491PMC
December 2017

Anti-SmD1 antibodies are associated with renal disorder, seizures, and pulmonary arterial hypertension in Chinese patients with active SLE.

Sci Rep 2017 08 8;7(1):7617. Epub 2017 Aug 8.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan, Beijing, 100730, China.

Detection of autoantibodies in systemic lupus erythematosus (SLE) plays an important role in timely diagnosis and earlier treatment of SLE. In this study, we used a SmD1 polypeptide-based ELISA to determine anti-SmD1 antibody in 269 SLE, including100 naïve (had not been treated with steroids or immunosuppressants at study inception) SLE patients and 169 non-naive SLE patients; 233 controls with other rheumatic diseases (RDC) (70 RA, 40 AS, 73SSc, and 50 SS), and 110 healthy controls (HC) group. The positive rate of anti-SmD1 among all SLE patients was 60.97%, higher than that in the RDC group (13.30%, P = 0.000) or the HC group (9.09%, P = 0.000). The positive rate of anti-SmD1 in non-naive SLE patients was higher than that for anti-dsDNA antibodies (44.97%, P = 0.03). Positivity for anti-SmD1 only was found in 14.00% of naive SLE patients and 16.00% of non-naive SLE patients. In naive SLE patients, the serum concentration of anti-SmD1 was lower after treatment than before treatment (P = 0.039). Active SLE patients positive for anti-SmD1 were more likely to have malar rash, rash, nonscarring alopecia, PAH and hypocomplementemia. High positivity for anti-SmD1 only in patients with SLE indicated the importance and necessity of detection of anti-SmD1 in patients with SLE.
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http://dx.doi.org/10.1038/s41598-017-08099-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548929PMC
August 2017

The Role of Anti-U1 RNP Positivity in Predicting Survival in Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: Angel or Demon? Comment on the Article by Sobanski et al.

Arthritis Rheumatol 2016 07;68(7):1788-9

Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.

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http://dx.doi.org/10.1002/art.39652DOI Listing
July 2016

Survival and prognostic factors of systemic lupus erythematosus-associated pulmonary arterial hypertension: A PRISMA-compliant systematic review and meta-analysis.

Autoimmun Rev 2016 Mar 27;15(3):250-7. Epub 2015 Nov 27.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China. Electronic address:

Objective: This study aims to evaluate the survival of patients with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) by a systematic review and meta-analysis.

Methods: Studies were searched from MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trial and Scopus databases, and were selected according to the inclusion and exclusion criteria. Two independent reviewers extracted data from selected studies. Quality assessments were also performed using the Newcastle-Ottawa Scale. All pooled analyses were conducted both for random-effects model and fixed-effects model. Subgroup analysis and sensitivity analysis were conducted to investigate the origins of heterogeneity. Publication bias was evaluated using Begg's funnel plots and Egger's test.

Results: Six studies encompassing 323 patients with SLE-associated PAH were included in the meta-analysis. The pooled 1-, 3- and 5-year survival rates were 88% (95% CI, 0.80-0.93), 81% (95% CI, 0.67-0.90) and 68% (95% CI, 0.52-0.80), respectively. No significant publication bias was shown. WHO Functional class (Fc) III/IV was found to be an independent prognostic factor of mortality. Higher mean pulmonary arterial pressure (mPAP), higher pulmonary vascular resistance (PVR), lower six minutes walking distance (6MWD), higher brain natriuretic peptide (BNP) and higher N-terminal proBNP (NT-proBNP) level were also related to poor survival.

Conclusion: The long-term survival of patients with SLE-associated PAH is poor, which is worth paying greater clinical and academic attention. This study suggested that early diagnosis and management are recommended in patients with SLE-associated PAH for a better outcome of survival.
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http://dx.doi.org/10.1016/j.autrev.2015.11.012DOI Listing
March 2016

Dr.VIS v2.0: an updated database of human disease-related viral integration sites in the era of high-throughput deep sequencing.

Nucleic Acids Res 2015 Jan 29;43(Database issue):D887-92. Epub 2014 Oct 29.

School of Life Sciences and Technology, Tongji University, Shanghai, China

Dr.VIS is a database of human disease-related viral integration sites (VIS). The number of VIS has grown rapidly since Dr.VIS was first released in 2011, and there is growing recognition of the important role that viral integration plays in the development of malignancies. The updated database version, Dr.VIS v2.0 (http://www.bioinfo.org/drvis or bminfor.tongji.edu.cn/drvis_v2), represents 25 diseases, covers 3340 integration sites of eight oncogenic viruses in human chromosomes and provides more accurate information about VIS from high-throughput deep sequencing results obtained mainly after 2012. Data of VISes for three newly identified oncogenic viruses for 14 related diseases have been added to this 2015 update, which has a 5-fold increase of VISes compared to Dr.VIS v1.0. Dr.VIS v2.0 has 2244 precise integration sites, 867 integration regions and 551 junction sequences. A total of 2295 integration sites are located near 1730 involved genes. Of the VISes, 1153 are detected in the exons or introns of genes, with 294 located up to 5 kb and a further 112 located up to 10 kb away. As viral integration may alter chromosome stability and gene expression levels, characterizing VISes will contribute toward the discovery of novel oncogenes, tumor suppressor genes and tumor-associated pathways.
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http://dx.doi.org/10.1093/nar/gku1074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383912PMC
January 2015

Spatiotemporal access model based on reputation for the sensing layer of the IoT.

ScientificWorldJournal 2014 6;2014:671038. Epub 2014 Aug 6.

Guangxi Key Laboratory of Trusted Software, Guilin University of Electronic Technology, Guilin 541004, China.

Access control is a key technology in providing security in the Internet of Things (IoT). The mainstream security approach proposed for the sensing layer of the IoT concentrates only on authentication while ignoring the more general models. Unreliable communications and resource constraints make the traditional access control techniques barely meet the requirements of the sensing layer of the IoT. In this paper, we propose a model that combines space and time with reputation to control access to the information within the sensing layer of the IoT. This model is called spatiotemporal access control based on reputation (STRAC). STRAC uses a lattice-based approach to decrease the size of policy bases. To solve the problem caused by unreliable communications, we propose both nondeterministic authorizations and stochastic authorizations. To more precisely manage the reputation of nodes, we propose two new mechanisms to update the reputation of nodes. These new approaches are the authority-based update mechanism (AUM) and the election-based update mechanism (EUM). We show how the model checker UPPAAL can be used to analyze the spatiotemporal access control model of an application. Finally, we also implement a prototype system to demonstrate the efficiency of our model.
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http://dx.doi.org/10.1155/2014/671038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142184PMC
May 2015

Genome-wide DNA methylation analysis identifies hypomethylated genes regulated by FOXP3 in human regulatory T cells.

Blood 2013 Oct 23;122(16):2823-36. Epub 2013 Aug 23.

The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;

Regulatory T cells (Treg) prevent the emergence of autoimmune disease. Prototypic natural Treg (nTreg) can be reliably identified by demethylation at the Forkhead-box P3 (FOXP3) locus. To explore the methylation landscape of nTreg, we analyzed genome-wide methylation in human naive nTreg (rTreg) and conventional naive CD4(+) T cells (Naive). We detected 2315 differentially methylated cytosine-guanosine dinucleotides (CpGs) between these 2 cell types, many of which clustered into 127 regions of differential methylation (RDMs). Activation changed the methylation status of 466 CpGs and 18 RDMs in Naive but did not alter DNA methylation in rTreg. Gene-set testing of the 127 RDMs showed that promoter methylation and gene expression were reciprocally related. RDMs were enriched for putative FOXP3-binding motifs. Moreover, CpGs within known FOXP3-binding regions in the genome were hypomethylated. In support of the view that methylation limits access of FOXP3 to its DNA targets, we showed that increased expression of the immune suppressive receptor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), which delineated Treg from activated effector T cells, was associated with hypomethylation and FOXP3 binding at the TIGIT locus. Differential methylation analysis provides insight into previously undefined human Treg signature genes and their mode of regulation.
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http://dx.doi.org/10.1182/blood-2013-02-481788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798997PMC
October 2013

T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10.

Nat Immunol 2013 Jul 19;14(7):741-8. Epub 2013 May 19.

Walter & Eliza Hall Institute of Medical Research, Parkville, Australia.

Functionally diverse T cell populations interact to maintain homeostasis of the immune system. We found that human and mouse antigen-activated T cells with high expression of the lymphocyte surface marker CD52 suppressed other T cells. CD52(hi)CD4(+) T cells were distinct from CD4(+)CD25(+)Foxp3(+) regulatory T cells. Their suppression was mediated by soluble CD52 released by phospholipase C. Soluble CD52 bound to the inhibitory receptor Siglec-10 and impaired phosphorylation of the T cell receptor-associated kinases Lck and Zap70 and T cell activation. Humans with type 1 diabetes had a lower frequency and diminished function of CD52(hi)CD4(+) T cells responsive to the autoantigen GAD65. In diabetes-prone mice of the nonobese diabetic (NOD) strain, transfer of lymphocyte populations depleted of CD52(hi) cells resulted in a substantially accelerated onset of diabetes. Our studies identify a ligand-receptor mechanism of T cell regulation that may protect humans and mice from autoimmune disease.
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http://dx.doi.org/10.1038/ni.2610DOI Listing
July 2013
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