Publications by authors named "Yin Su"

94 Publications

The characteristics and its contributing factors of refractory rheumatoid arthritis, view of the rheumatologists of China: results of a nationwide cross-sectional survey.

Clin Rheumatol 2021 May 3. Epub 2021 May 3.

Department of Rheumatology and Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100044, China.

Objective: To explore the characteristics of refractory RA and its contributory factors based on the understanding of the rheumatologists of China.

Methods: A national cross-sectional survey was performed in 32 provinces across China, and 1381 rheumatologists were recruited. Information about the sociodemographic background, refractory RA characteristics, and contributory factors was collected using a pre-made questionnaire including fourteen single-choice and four multiple-choice questions, respectively. Each of the single-choice and multiple-choice question had several items.

Results: In response to the single-choice questions regarding the definition of refractory RA, 52.28% responded that "the 28 joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) > 5.1 with presence of signs suggestive of inflammatory disease" is characteristic of refractory RA, whereas 50.18% opined that "If target was not achieved with 2 conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) combined with 1 biological or 1 targeted synthetic DMARD (b/tsDMARD), over a total of 3~6 months" should be considered refractory RA. In addition, 39.32% rheumatologists were in favor of inability to taper glucocorticoids (GCs) ≤ 10mg prednisone or equivalent daily. Additional features considered characteristics of refractory RA were extra-articular manifestations (84.94%), interfering comorbidities (76.32%), and radiographic progression (71.83%). Among the contributory factors, 92.03% considered infection, and interstitial lung disease was chosen by 90.95%, vasculitis by 82.26%, osteoporosis by 70.67%, and fibromyalgia syndrome by 70.38%.

Conclusions: Our survey has demonstrated a variety of concepts of refractory RA among the rheumatologists of China. Disease activity assessment, treatment options, interfering comorbidities, and radiological progression all were associated with the characteristics of refractory RA. Key Points • This study demonstrated the definition, characteristics, and contributing factors of refractory RA from the rheumatologists' views in China. • The clarification of the insights and concepts on refractory RA will help to make comprehensive guidelines to treat this disease, further improving prognosis and reducing the societal burdens of RA.
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http://dx.doi.org/10.1007/s10067-021-05687-7DOI Listing
May 2021

Clinical features and relapse risks of IgG4-related ophthalmic disease: a single-center experience in China.

Arthritis Res Ther 2021 03 31;23(1):98. Epub 2021 Mar 31.

Department of Rheumatology and Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100044, China.

Background: IgG4-related ophthalmic disease (IgG4-ROD) is one of the phenotypes of IgG4-related disease (IgG4-RD), and its lesions are mainly located in the ocular. Currently, there are few studies on IgG4-ROD and no study has compared the phenotypic differences between IgG4-ROD and non IgG4-ROD (nIgG4-ROD). Thus, it is difficult to establish the optimal treatment strategy for IgG4-ROD. The aim of this study was to identify the disparities between the two groups and to clarify the risk factors for IgG4-ROD relapse.

Methods: 434 IgG4-RD patients met comprehensive diagnostic criteria and diagnosed at Peking University People's Hospital between January 2009 and January 2020 were recruited in this study. Patients were divided into IgG4-ROD and nIgG4-ROD group according to the ophthalmic involvement. Demographic, clinical, and laboratory data of two groups were collected and compared. Cox regression analysis was used to identify the independent risk factors for IgG4-ROD relapse.

Results: 255 IgG4-ROD patients were identified in this study. IgG4-ROD group had almost equal sex ratio, younger age of disease onset and diagnosis comparing with nIgG4-ROD patients. As compared to nIgG4-ROD group, higher percentage of IgG4-ROD patients met the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria (AECC) for IgG4-RD; moreover, IgG4-ROD patients had higher AECC scores and IgG4-RD responder index (RI). Allergic diseases and multiorgan involvement were more common in IgG4-ROD group. IgG4-ROD was frequently associated with salivary gland, paranasal sinus, lung, and lymph node involvement, while retroperitoneal fibrosis and biliary system lesions were more common in nIgG4-ROD. IgG4-ROD patients had higher serum IgG4 levels, IgG4/IgG ratio, IgE levels, and lower CRP levels. The initial glucocorticoid plus immunosuppressant was a protective factor for IgG4-ROD relapse. IgG4-ROD patients treated with initial glucocorticoid plus immunosuppressant had longer relapse-free survival time than patients treated with initial glucocorticoid monotherapy.

Conclusions: IgG4-ROD patients had distinctive clinical features compared with nIgG4-ROD patients. The initial glucocorticoid plus immunosuppressant was a protective factor for IgG4-ROD relapse, which could prolong the relapse-free survival time of IgG4-ROD patients. These findings may have important implications for understanding and management of IgG4-ROD.
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http://dx.doi.org/10.1186/s13075-021-02489-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011084PMC
March 2021

Use of Wise Device Technology to Measure Adherence to Hydroxyurea Therapy in Youth With Sickle Cell Disease.

J Pediatr Hematol Oncol 2021 01;43(1):e19-e25

Hematology, St. Jude Children's Research Hospital, Memphis, TN.

Despite broad support for hydroxyurea (HU) therapy, suboptimal adherence is reported for youth with sickle cell disease. Valid adherence measurement is crucial to understanding the relationship between medication behavior, disease response, and patient-centered health outcomes. The current pilot study examined the feasibility of the Wise electronic device for longitudinal HU adherence measurement in a sample of 36 youths prescribed HU. The study also explored the association between HU adherence, as measured by the Wise device, with other adherence measures (ie, family report, lab values, pill count, and medication possession ratio). A measure of family-reported acceptability was also completed. Overall, results supported the feasibility of the Wise device (rate of consent=82%, device use=75%, device failure=3%) for HU adherence measurement and most families rated their experience using their device positively (favorable responses ranged from 67% to 100%). Associations between HU adherence, as measured by the Wise device, and other adherence measures were not significant. Overall, the feasibility was supported. The Wise device allows longitudinal measurement of adherence with HU from initiation as a young child (ie, with liquid formulations) through adolescence and provides a novel means of adherence measurement for both clinical and research use.
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http://dx.doi.org/10.1097/MPH.0000000000001997DOI Listing
January 2021

Psychosocial Factors and Psychological Interventions: Implications for Chronic Post-Surgical Pain in Pediatric Patients with Osteosarcoma.

J Clin Psychol Med Settings 2020 Nov 10. Epub 2020 Nov 10.

Division of Anesthesiology, Department of Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA.

This study retrospectively investigated psychological factors contributing to chronic post-surgical pain (CPSP) in pediatric patients after limb-sparing or amputation surgery for extremity osteosarcoma. Psychological factors were identified and analyzed by the Wilcoxon rank-sum and median two-sample tests. Univariate and multivariate Cox regressions were performed using gender, age, psychological factors, and psychological interventions related to CPSP duration as covariates. Duration of pain treatment was significantly longer in patients resistant to psychological interventions (p = 0.01) than those receptive to interventions. Shorter duration of pain treatment was associated with older age (p = 0.03) and receptiveness to psychological interventions (HR = 4.19, 95% CI [1.22, 14.35]). Older age and receptiveness to psychological interventions as part of pain management care are associated with needing a shorter duration of pain treatment. Our results highlight the importance of prospective investigations evaluating motivation to engage in psychotherapy and psychological interventions and identify risk factors for CPSP in pediatric oncology.
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http://dx.doi.org/10.1007/s10880-020-09748-yDOI Listing
November 2020

CD14CD16 monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK.

Arthritis Res Ther 2020 09 21;22(1):221. Epub 2020 Sep 21.

Department of Rheumatology and Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100044, China.

Background: Monocytes as precursors of osteoclasts in rheumatoid arthritis (RA) are well demonstrated, while monocyte subsets in osteoclast formation are still controversial. Tyro3 tyrosine kinase (Tyro3TK) is a member of the receptor tyrosine kinase family involved in immune homeostasis, the role of which in osteoclast differentiation was reported recently. This study aimed to compare the osteoclastic capacity of CD14CD16 and CD14CD16 monocytes in RA and determine the potential involvement of Tyro3TK in their osteoclastogenesis.

Methods: Osteoclasts were induced from CD14CD16 and CD14CD16 monocyte subsets isolated from healthy control (HC) and RA patients in vitro and evaluated by tartrate-resistant acid phosphatase (TRAP) staining. Then, the expression of Tyro3TK on CD14CD16 and CD14CD16 monocyte subsets in the peripheral blood of RA, osteoarthritis (OA) patients, and HC were evaluated by flow cytometry and qPCR, and their correlation with RA patient clinical and immunological features was analyzed. The role of Tyro3TK in CD14CD16 monocyte-mediated osteoclastogenesis was further investigated by osteoclast differentiation assay with Tyro3TK blockade.

Results: The results revealed that CD14CD16 monocytes were the primary source of osteoclasts. Compared with HC and OA patients, the expression of Tyro3TK on CD14CD16 monocytes in RA patients was significantly upregulated and positively correlated with the disease manifestations, such as IgM level, tender joint count, and the disease activity score. Moreover, anti-Tyro3TK antibody could inhibit Gas6-mediated osteoclast differentiation from CD14CD16 monocytes in a dose-dependent manner.

Conclusions: These findings indicate that elevated Tyro3TK on CD14CD16 monocytes serves as a critical signal for osteoclast differentiation in RA.
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http://dx.doi.org/10.1186/s13075-020-02308-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507256PMC
September 2020

Anti-recoverin antibodies indicate fundus abnormalities in systemic lupus erythematosus.

Lupus 2020 Oct 23;29(11):1346-1352. Epub 2020 Jul 23.

Department of Rheumatology and Immunology, 12465Peking University People's Hospital, Beijing, China.

Objectives: Lupus fundus abnormalities are a sight-threatening complication of systemic lupus erythematosus (SLE) and its pathogenesis remains to be studied. The aim of this study was to assess the clinical characteristics associated with the presence of anti-recoverin antibodies in patients with SLE, especially those with fundus abnormalities.

Methods: Seventy-six participants were enrolled, including 21 patients with fundus abnormalities (fundus group), 30 patients without fundus abnormalities (non-fundus group) and 25 healthy individuals. Serum anti-recoverin antibody levels were measured using enzyme-linked immunosorbent assay, and clinical and laboratory data were obtained from medical records.

Results: Compared with the non-fundus group, the fundus group had a higher incidence of hematuria ( < 0.05). The Systemic Erythematosus Disease Activity Index (SLEDAI) score in the fundus group was significantly higher than the non-fundus group (21.48 ± 8.06 versus 10.80 ± 5.74,  < 0.001). The levels of serum anti-recoverin antibodies in the fundus group were significantly higher than the non-fundus group ( = 0.029) or the healthy control group ( = 0.011). Anti-recoverin-negative and -positive patients differed on a number of clinical parameters, including incidence of fever, rash, antinuclear antibody, anti-dsDNA antibody, erythrocyte sedimentation rate, immunoglobulin G, complement C3 and complement C4. The average SLEDAI score of anti-recoverin-positive patients was significantly higher than anti-recoverin-negative patients (17.73 ± 8.11 versus 12.56 ± 8.37,  < 0.05).

Conclusions: Anti-recoverin antibodies were related to higher disease activities in SLE, especially those with fundus abnormalities, suggesting that anti-recoverin antibodies may play an important role in the pathogenesis of fundus abnormalities in SLE.
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http://dx.doi.org/10.1177/0961203320940780DOI Listing
October 2020

Influence of γ-irradiation and oxygen conditions on the diffusion of I-125 in crushed Beishan granite.

Appl Radiat Isot 2020 Sep 21;163:109224. Epub 2020 May 21.

Radiochemistry Lab, School of Nuclear Science and Technology, Lanzhou University, 730000, Lanzhou, PR China; Key Laboratory of Special Function Materials and Structure Design, Ministry of Education, Lanzhou University, 730000, Lanzhou, PR China. Electronic address:

The diffusion of iodine (labeled with I) in compacted Beishan granite (BsG) was investigated using the in-diffusion capillary method at pH ~2.0 to ~11.0 under oxygen and irradiation conditions. With the advantages of simple and easy operation of the capillary diffusion devices, this work makes a preliminary investigation on the irradiation condition that cannot be performed by the traditional diffusion experiment. In this study, D values of I as a tracer in the form of iodide were determined to investigate and assess the influence of irradiation and oxygen conditions, which must be considered in-situ environment of the geologic repository. The results indicate that capillary method is a simple and efficient method to study the diffusion behavior of radionuclides, which is a relatively feasible to quickly obtain the diffusion coefficient, especially for some special conditions, e.g., oxygen and irradiation conditions. The diffusion results showed that D values of I range from 1.4 × 10 to 1.5 × 10 m∙s, which was much faster than other nuclides, such as Se (10 m∙s). The batch adsorption experiments in this paper and related studies showed that the sorption could be neglected, i.e., I is a weak adsorbent nuclide. Its diffusion and sorption process were hardly affected by pH、oxygen and irradiation conditions, which is very different from Se. Besides, ionic strength has a significant impact on the diffusion rate of I, which is closely related to the double electric layer. Overall, this study indicates that natural BsG couldn't greatly attenuate the mobility of I in the deep geologic repository and new retardation method or materials need to be explored.
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http://dx.doi.org/10.1016/j.apradiso.2020.109224DOI Listing
September 2020

Rothia mucilaginosa Infections in Pediatric Cancer Patients.

J Pediatric Infect Dis Soc 2021 Apr;10(3):341-344

Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee, USA.

We performed a retrospective study to determine the epidemiology of Rothia mucilaginosa infections among pediatric cancer patients. Over 20 years, 37 cases were identified; 27% developed complications, but there was no infection-related mortality. All cases were successfully treated with vancomycin.
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http://dx.doi.org/10.1093/jpids/piaa047DOI Listing
April 2021

Scavenger receptor-A is a biomarker and effector of rheumatoid arthritis: A large-scale multicenter study.

Nat Commun 2020 04 20;11(1):1911. Epub 2020 Apr 20.

Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.

Early diagnosis is critical to improve outcomes in rheumatoid arthritis (RA), but current diagnostic tools have limited sensitivity. Here we report a large-scale multicenter study involving training and validation cohorts of 3,262 participants. We show that serum levels of soluble scavenger receptor-A (sSR-A) are increased in patients with RA and correlate positively with clinical and immunological features of the disease. This discriminatory capacity of sSR-A is clinically valuable and complements the diagnosis for early stage and seronegative RA. sSR-A also has 15.97% prevalence in undifferentiated arthritis patients. Furthermore, administration of SR-A accelerates the onset of experimental arthritis in mice, whereas inhibition of SR-A ameliorates the disease pathogenesis. Together, these data identify sSR-A as a potential biomarker in diagnosis of RA, and targeting SR-A might be a therapeutic strategy.
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http://dx.doi.org/10.1038/s41467-020-15700-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171100PMC
April 2020

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis.

Chin Med J (Engl) 2019 Dec;132(24):2899-2904

Department of Rheumatology and Immunology, Hebei General Hospital, Shijiazhuang, Hebei 050051, China.

Background: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.

Methods: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.

Results: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001).

Conclusion: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.
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http://dx.doi.org/10.1097/CM9.0000000000000570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964957PMC
December 2019

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial.

Ann Rheum Dis 2020 01 19;79(1):141-149. Epub 2019 Sep 19.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China

Objectives: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy.

Methods: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets.

Results: At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells.

Conclusions: Low-dose IL-2 might be effective and tolerated in treatment of SLE.

Trial Registration Number: ClinicalTrials.gov Registries (NCT02465580 and NCT02932137).
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http://dx.doi.org/10.1136/annrheumdis-2019-215396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937406PMC
January 2020

General One-step Synthesis of Symmetrical or Unsymmetrical 1,4-Di(organo)fullerenes from Organo(hydro)fullerenes through Direct Oxidative Arylation.

J Org Chem 2019 Oct 6;84(19):12259-12267. Epub 2019 Aug 6.

State Key Lab for Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemistry, College of Chemistry and Chemical Engineering , Xiamen University , Xiamen 361005 China.

A general one-step synthesis of symmetrical or unsymmetrical 1,4-di(organo)fullerenes from organo(hydro)fullerenes (RCH) is realized by direct oxidative arylation. The new combination of catalytic trifluoromethanesulfonic acid (TfOH) and stoichiometric -chloranil is the first to be used to directly generate an R-C intermediate from common RCH. Unexpectedly, the in situ generated R-C intermediate is shown to be quite stable in whole C NMR spectroscopy characterization in the absence of cation quenching reagents. Because the direct oxidation of common RCH to form the corresponding R-C has never been realized, the present combination of TfOH and -chloranil solves the challenges associated with the formation of stable RC cations from common RCH without any coordination of an R group.
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http://dx.doi.org/10.1021/acs.joc.9b01272DOI Listing
October 2019

A Survey-based Study of Pharmacist Acceptance and Resistance to Health Information Technology.

Perspect Health Inf Manag 2019 1;16(Spring):1a. Epub 2019 Apr 1.

The University of Tennessee Health Science Center in Memphis, TN.

Purpose: Because user acceptance and resistance to the use of health information technology (HIT) affects system utilization and previous studies in this area have typically excluded pharmacists, this study specifically addresses the response of institutional pharmacists to HIT.

Methods: A survey investigating pharmacists' responses to electronic medical record (EMR) system use was developed using questions modified from previously validated research. The survey was distributed electronically to the mailing list for pharmacy preceptors for the University of Tennessee College of Pharmacy. Descriptive statistics and univariate and multivariate analyses were used to analyze the collected data based on a previously validated dual-factor model.

Results: Of the 96 responses from institutional pharmacists, 64 responses (66.7 percent) were complete and usable. Of the acceptance and resistance constructs evaluated, only attitude and perceived behavior control were found to be significantly associated with acceptance of use ( = .036 and = .025, respectively), and only transition cost was found to be significantly associated with resistance to use ( = .018). System vendor and interface integration were also significantly associated with acceptance of use. These findings suggest that attitude, perceived behavior control, and transition costs may have the most impact on pharmacists' responses to the use of EMR systems.

Conclusion: It is reasonable for hospitals to focus efforts on specific factors influencing acceptance of and resistance to EMR use and, before a system is selected, to consider the effects of vendor selection and level of interface integration on acceptance of use.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462883PMC
March 2020

Sequencing of the MHC region defines as the major genetic risk for seropositive rheumatoid arthritis in Han Chinese population.

Ann Rheum Dis 2019 06 1;78(6):773-780. Epub 2019 Apr 1.

BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Peking-Tsinghua Center for Life Sciences at College of Chemistry and Molecular Engineering, and Center for Quantitative Biology, Peking University, Beijing, China.

Objective: The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen (. However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC.

Methods: We first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case-control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants.

Results: HLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10, OR=2.29). DRβ1:37N had an independent protective effect (p=5.81×10, OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRβ1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.

Conclusions: We provide the first evidence that HLA-DQα1:160D, instead of , is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.
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http://dx.doi.org/10.1136/annrheumdis-2018-214725DOI Listing
June 2019

Prevalence and characteristics of acute respiratory virus infections in pediatric cancer patients.

J Med Virol 2019 07 27;91(7):1191-1201. Epub 2019 Feb 27.

Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut Faculty of Medicine, Beirut, Lebanon.

Background: Patients with pediatric cancer have a higher risk of morbidity and mortality because of respiratory viral infections than other patient populations.

Objectives: To investigate the causative viruses of respiratory infections and their burden among patients with pediatric cancer in Lebanon.

Study Design: Nasopharyngeal swabs along with clinical and demographic data were collected from patients with pediatric cancer presenting febrile episodes with upper respiratory tract symptoms. Total nucleic acid was extracted from specimens followed by the real-time PCR analysis targeting 14 respiratory viruses to estimate the frequency of infections.

Results: We obtained 89 nasopharyngeal swabs from patients with pediatric cancer (mean age, 5.8 ± 4.2 years). Real-time PCR confirmed viral infection in 77 swabs (86.5%). Among these, 151 respiratory viruses were detected. Several viruses cocirculated within the same period; respiratory syncytial virus (RSV) being the most common (45.45%), followed by parainfluenza virus (PIV; 26%), influenza type B (26%), human metapneumovirus (24.6%), and human coronavirus (HCoV; 24.6%). Coinfections were detected in 55% of the subjects, and most of them involved RSV with one or more other viruses. A strong correlation was found between PIV, Flu (influenza of any type), RSV, and HCoV with the incidence of coinfections. RSV was associated with lower respiratory tract infections, nasal congestion, bronchitis, and bacteremia. HCoV was associated with bronchiolitis; rhinovirus was associated with hospital admission.

Conclusion: Patients with pediatric cancer have a high burden of respiratory viral infections and a high incidence of coinfections. Molecular diagnostics can improve management of febrile episodes and reduce antibiotic use.
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http://dx.doi.org/10.1002/jmv.25432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166696PMC
July 2019

Efficacy and Safety of Recombinant Activated Factor VII Off-label Use in a Pediatric Hematology/Oncology Cohort.

J Pediatr Hematol Oncol 2019 03;41(2):e72-e78

Departments of Hematology.

Background: Recombinant activated factor VII (rFVIIa) has been used off-label to treat or prevent severe bleeding in patients for whom conventional treatments are unsuccessful. However, studies in children remain limited.

Procedure: To examine the efficacy and safety of rFVIIa, we performed a retrospective analysis of rFVIIa off-label use in a pediatric hematology/oncology cohort at a single center from 2006 to 2014.

Results: Of 58 patients identified, 46 (79.3%) received rFVIIa to treat bleeding and 12 (20.7%) to prevent bleeding. Thirty-three (71.7%) patients had life-threatening bleeding. In the treatment group, 63.0% patients were responders (ie, bleeding decreased or stopped) and 37.0% were nonresponders (ie, bleeding did not change). Blood products usage was similar between responders and nonresponders. After rFVIIa administration, prothrombin time, partial thromboplastin time and lactate were significantly lower, but fibrinogen was significantly higher in responders than nonresponders. Venous thromboembolism developed in 5.2% (3/58) patients, but its relation to rFVIIa remains unclear. Responders had significantly lower mortality than nonresponders (17.2% vs. 82.4%, P<0.0001).

Conclusions: rFVIIa controlled most bleeding events in this cohort, despite predominance of life-threatening bleeding, suggesting good efficacy. Venous thromboembolism rate was low. Further studies are warranted to identify predictors of favorable response to rFVIIa in similar patients.
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http://dx.doi.org/10.1097/MPH.0000000000001379DOI Listing
March 2019

Association between Physical Activity and Higher Serum Creatinine/Uric Acid by Dose-response Association.

Biomed Environ Sci 2018 Oct;31(10):769-772

School of Public Health, North China University of Science and Technology, Tangshan 063210, Hebei, China.

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http://dx.doi.org/10.3967/bes2018.102DOI Listing
October 2018

Disability and health-related quality of life in Chinese patients with rheumatoid arthritis: A cross-sectional study.

Int J Rheum Dis 2018 Sep;21(9):1709-1715

Department of Rheumatology and Immunology, The People's Hospital of Hebei Province, Shijiazhuang, China.

Aim: The objective of this study was to evaluate the impact of rheumatoid arthritis (RA) on physical function and health-related quality of life (HRQoL) in China.

Method: A cross-section survey was conducted in 21 general hospitals in China. Eight hundred and seven patients were recruited. Data on demographics, clinical data, physical function (Stanford Health Assessment Questionnaire Disability Index, HAQ-DI) and HRQoL (Study Short Form 36 Health Survey, SF-36) were collected on site.

Results: In our cohort, physical function was impaired in 77.6% of patients (HAQ-DI >0). The median (interquartile range, IQR) of HAQ-DI was 0.750 (0.125, 1.500). Rated by HAQ-DI 0-1, >1-2, and >2-3, percentage of patients with mild, moderate and severe disability was 61.0%, 25.4%, and 13.6%, respectively. Older age, long disease duration, presence of extra-articular manifestations, tender joint count (TJC), overall status (assessed by patient Global Visual Analogue Scale [G-VAS] and physician G-VAS) and lacking disease-modifying anti-rheumatic drugs were identified as predictive factors for worse physical function (P < .05). The composite scores of SF-36 in the observed patients were: physical component summary 40.4 (IQR 27.4, 60.3), and mental component summary 49.0 (IQR 33.6, 70.9). Impaired physical health may be predicted by low income, presence of extra-articular manifestations, TJC, patient G-VAS and high HAQ-DI. Predictors for suboptimal mental health were low income, physical labor, married status, increased swollen joint count (SJC), physician G-VAS and high HAQ-DI.

Conclusion: Rheumatoid arthritis has profound effects on physical function and HRQoL in Chinese patients. Patients with identified predictive factors for poor outcome should be closely monitored.
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http://dx.doi.org/10.1111/1756-185X.13345DOI Listing
September 2018

Brown Recluse Spider Bites in Patients With Neutropenia: A Single-institution Experience.

J Pediatr Hematol Oncol 2019 01;41(1):28-33

Departments of Infectious Diseases.

Brown recluse spider bites can cause local and systemic signs, including rash, dermonecrosis, edema, hemolysis, and acute kidney failure. These are mostly attributed to sphingomyelinase D, the main toxin. To evaluate the severity of the disease in pediatric patients with and without neutropenia, we retrospectively reviewed records of patients treated at St. Jude Children's Research Hospital between 1970 and 2015 and identified 19 patients who met the inclusion criteria. Variables of interest included the type of underlying illness, presence of neutropenia, number of days of hospitalization, disease signs and outcome of the bite, and treatments administered. We used descriptive statistics to summarize the manifestations and severity of spider bites in patients with and without neutropenia. Six patients experienced pain from the bite, 11 had erythema, 7 developed edema, and 5 had fever. The response to spider bites in neutropenic patients was no milder than that in non-neutropenic individuals. Six patients developed systemic complications. Compared with non-neutropenic patients, neutropenic patients had antibiotics prescribed more often and experienced longer hospital stays. Spider bites do not seem to have a different clinical course in neutropenic patients. Therefore, a conservative approach may be best for these patients, with close monitoring and local wound care.
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http://dx.doi.org/10.1097/MPH.0000000000001253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295234PMC
January 2019

Early application of continuous high-volume haemofiltration can reduce sepsis and improve the prognosis of patients with severe burns.

Crit Care 2018 07 6;22(1):173. Epub 2018 Jul 6.

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Background: In the early stage of severe burn, patients often exhibit a high level of inflammatory mediators in blood and are likely to develop sepsis. High-volume haemofiltration (HVHF) can eliminate these inflammatory mediators. We hypothesised that early application of HVHF may be beneficial in reducing sepsis and improving the prognosis of patients with severe burns.

Methods: Adults patients with burns ≥ 50% total burn surface area (TBSA) and in whom the sum of deep partial and full-thickness burn areas was ≥ 30% were enrolled in this randomised prospective study, and they were divided into control (41 cases) and HVHF (41 cases) groups. Patients in the control group received standard management for major burns, whereas the HVHF group additionally received HVHF treatment (65 ml/kg/h for 3 consecutive days) within 3 days after burn. The incidence of sepsis and mortality, some laboratory data, levels of inflammatory cytokines in the blood, HLA-DR expression on CD14 peripheral blood monocytes, the proportion of CD25Foxp3 in CD4 T lymphocytes, and the counts of CD3, CD4 and CD8 T lymphocytes were recorded within 28 days post-burn.

Results: The incidence of sepsis, septic shock and duration of vasopressor treatment were decreased significantly in the HVHF group. In addition, in the subgroup of patients with burns ≥ 80% TBSA, the 90-day mortality showed significant decreases in the HVHF group. The ratio of arterial oxygen partial pressure to the fraction of inspiration oxygen was improved after HVHF treatment. In the patients who received HVHF treatment, the blood levels of inflammatory cytokines, including tumour necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8, as well as the blood level of procalcitonin were found to be lower than in the control group. Moreover, higher HLA-DR expression on CD14 monocytes and a lower proportion of CD25Foxp3 in CD4 T lymphocytes were observed in the patients in the HVHF group.

Conclusions: Early application of HVHF benefits patients with severe burns, especially for those with a greater burn area (≥ 80% TBSA), decreasing the incidence of sepsis and mortality. This effect may be attributed to its early clearance of inflammatory mediators and the recovery of the patient's immune status.

Trial Registration: Chinese Clinical Trial Register, ChiCTR-TRC-12002616 . Registered on 24 October 2012.
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http://dx.doi.org/10.1186/s13054-018-2095-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035411PMC
July 2018

Patient factors associated with sperm cryopreservation among at-risk adolescents newly diagnosed with cancer.

Cancer 2018 09 5;124(17):3567-3575. Epub 2018 Jul 5.

Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, Texas (retired).

Background: Although survivors of adolescent-onset cancers are at risk of infertility, the majority desire children. Fertility preservation options are available for adolescents, but sperm banking remains underused. To the authors' knowledge, patient factors that influence decisions to bank sperm are poorly understood.

Methods: A cross-sectional study of 146 adolescent males who were newly diagnosed with cancer and who completed surveys within 1 week of treatment initiation was performed. Participants, 65% of whom were white, were aged 13 to 21 years (mean, 16.49 years; standard deviation, 2.02 years) and were at risk of infertility secondary to impending gonadotoxic treatment. Participating institutions included 8 leading pediatric oncology centers across the United States and Canada.

Results: Of the patients approached, approximately 80.6% participated. Parent recommendation to bank (odds ratio [OR], 4.88; 95% confidence interval [95% CI], 1.15-20.71 [P = .03]), higher Tanner stage (OR, 4.25; 95% CI, 1.60-11.27 [P < .01]), greater perceived benefits (OR, 1.41; 95% CI, 1.12-1.77 [P < .01]), and lower social barriers to banking (OR, 0.88; 95% CI, 0.81-0.96 [P < .01]) were found to be associated with adolescent collection attempts, whereas meeting with a fertility specialist (OR, 3.44; 95% CI, 1.00-11.83 [P = .05]), parent (OR, 3.02; 95% CI, 1.12-8.10 [P = .03]) or provider (OR, 2.67; 95% CI, 1.05-6.77 [P = .04]) recommendation to bank, and greater adolescent self-efficacy to bank (OR, 1.16; 95% CI, 1.01-1.33 [P = .03]) were found to be associated with successful sperm banking.

Conclusions: Adolescents' perceived benefits of sperm banking, higher Tanner stage, and parent recommendation were associated with collection attempts, whereas perceived social barriers decreased this likelihood. Successful banking was associated with greater adolescent self-efficacy, parent and provider recommendation to bank, and consultation with a fertility specialist. Providers should consult with both adolescents and parents regarding fertility preservation, and interventions should be tailored to address barriers to sperm banking while promoting its benefits.
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http://dx.doi.org/10.1002/cncr.31596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191330PMC
September 2018

Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial.

Lancet Infect Dis 2018 08 5;18(8):854-863. Epub 2018 Jun 5.

Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.

Background: Central line-associated bloodstream infections (CLABSIs) affect about 25% of children with cancer, and treatment failure is common. Adjunctive ethanol lock therapy might prevent treatment failure but high-quality evidence is scarce. We evaluated ethanol lock therapy as treatment and secondary prophylaxis for CLABSI in children with cancer or haematological disorders.

Methods: This randomised, double-blind, placebo-controlled superiority trial, with two interim futility and efficacy analyses (done when the first 46 and 92 evaluable participants completed study requirements), was done at two paediatric hospitals in the USA and Australia. Patients aged 6 months to 24 years, inclusive, with cancer or a haematological disorder and new CLABSI were eligible. Participants were randomly assigned (1:1) to receive either ethanol lock therapy (70% ethanol) or placebo (heparinised saline) for 2-4 h per lumen daily for 5 days (treatment phase), then for up to 3 non-consecutive days per week for 24 weeks (prophylaxis phase). The primary composite outcome was treatment failure, consisting of attributable catheter removal or death, new or persistent (>72 h) infection, or additional lock therapy during the treatment phase, and recurrent CLABSI during the prophylaxis phase. This trial is registered with ClinicalTrials.gov, number NCT01472965.

Findings: 94 evaluable participants were enrolled between Dec 14, 2011, and Sept 12, 2016, of whom 48 received ethanol lock therapy and 46 received placebo. The study met futility criteria at the second interim analysis. Treatment failure was similar with ethanol lock therapy (21 [44%] of 48) and placebo (20 [43%] of 46; relative risk [RR] 1·0, 95% CI 0·6-1·6; p=0·98). Some adverse events, including infusion reactions and catheter occlusion, were more frequent in the ethanol lock therapy group than in the placebo group. Catheter occlusion requiring thrombolytic therapy was more common with ethanol lock therapy (28 [58%] of 48) than with placebo (15 [33%] of 46; RR 1·8, 95% CI 1·1-2·9; p=0·012). Discontinuation of lock therapy because of adverse effects or patient request occurred in a similar proportion of participants in the ethanol lock therapy (nine [19%] of 48) and placebo groups (ten [22%] of 46; p=0·72).

Interpretation: Ethanol lock therapy did not prevent CLABSI treatment failure and it increased catheter occlusion. Routine ethanol lock therapy for treatment or secondary prophylaxis is not recommended in this population.

Funding: American Lebanese Syrian Associated Charities to St Jude Children's Research Hospital and an Australian Government Research Training Scholarship.
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http://dx.doi.org/10.1016/S1473-3099(18)30224-XDOI Listing
August 2018

Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance.

Sci Rep 2018 05 23;8(1):8048. Epub 2018 May 23.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.

Although rare variant C1Q deficiency was identified as causative risk for systemic lupus erythematosus (SLE), there are limited and inconsistent reports regarding the common polymorphisms of C1Q genes in SLE susceptibility. Furthermore, there are no reports concerning polymorphisms of C1S, C1R, and C1RL and whether they confer susceptibility to SLE. We therefore evaluated 22 SNPs across six C1-complex genes in two independent case-control cohorts, and identified four novel SNPs that confer protection from SLE. The four SNPs are all located in C1Q. Particularly, the variant rs653286 displayed an independent reduced risk on SLE susceptibility (OR 0.75, P = 2.16 × 10) and anti-dsDNA antibodies (OR 0.68, P = 0.024). By bioinformatics analysis, SNPs rs653286 and rs291985 displayed striking cis-eQTL effects on C1Q genes expression. Individuals homozygous for the 'protective' allele at four SNPs had significantly higher levels of serum C1q (rs680123-rs682658: P = 0.0022; rs653286-rs291985: P = 0.0076). To our knowledge, this is the first study to demonstrate that only C1Q polymorphisms are associated with SLE. The C1Q SNP rs653286 confers an independent protective effect on SLE susceptibility and affects transcript abundance.
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http://dx.doi.org/10.1038/s41598-018-26380-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966390PMC
May 2018

Monoclonal gammopathy in rheumatic diseases.

Clin Rheumatol 2018 Jul 13;37(7):1751-1762. Epub 2018 Mar 13.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.

To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P = 0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P = 0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P = 0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P = 0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015-1.251), P = 0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011-1.242), P = 0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype switch, 1 progressed to multiple myeloma (MM), and another 2 experienced renal injuries attributed by monoclonal or polyclonal plasma cell interstitial infiltration. Seven (17.1%) of the 41 MG patients presented hematological neoplasias, 4 with MM, 2 with smoldering multiple myeloma, and 1 with B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The presence of light-chain MG was associated with the development of MM [OR 17.5 (95%CI 1.551-197.435), P = 0.041], but not with an increased risk of lymphoma or SMM. MG was observed in patients with various rheumatic disorders, with SS being the most common type. The presence of MG might be associated with higher disease activity. The development of hematological neoplasias including MM and lymphoma was seen in this setting. Therefore, we recommend the screening for MG and close monitoring for potential malignant transformation in patients with rheumatic diseases as needed.
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http://dx.doi.org/10.1007/s10067-018-4064-8DOI Listing
July 2018

Contribution of the α5 GABAA receptor to the discriminative stimulus effects of propofol in rat.

Neuroreport 2018 03;29(5):347-352

Department of Anesthesiology, Second Affiliated Hospital and Institute of Neuroendocrinology, Wenzhou Medical University, Wenzhou.

Propofol as an agonist of GABAA receptor has a rewarding and discriminative stimulus effect. However, which subtype of the GABAA receptor is involved in the discriminative stimulus effects of propofol is still not clear. We observed the effects of an agonist or an antagonist of the subtype-selective GABAA receptor on discriminative stimulus effects of propofol. Male Sprague-Dawley rats were trained to discriminate 10 mg/kg (intraperitoneal) propofol from intralipid under a fixed-ratio 10 schedule of food reinforcement. We found that propofol produced dose-dependent substitution for propofol at 10 mg/kg, with response rate reduction only at a dose above those producing the complete substitution. CL218,872 (1-3 mg/kg, intraperitoneal), an α1 subunit-selective GABAA receptor agonist, and SL651,498 (0.3-3 mg/kg, intraperitoneal), an α2/3 GABAA receptor selective agonist, could partially substitute for the discriminative stimulus effects of propofol (40-80% propofol-appropriate responding). Meanwhile, L838,417 (0.2-0.6 mg/kg, intravenous), a α2/3/5 GABAA receptor selective agonist, could produce near 100% propofol-appropriate responding and completely substitute for propofol effects. Moreover, the administration of L655,708, the α5 GABAA receptor inverse agonist, could dose dependently attenuate the discriminative stimulus of propofol. In contrast, the α1 GABAA receptor antagonist β-CCt (1-3 mg/kg) combined with propofol (10 mg/kg) failed to block the propofol effect. The data showed that propofol produces discriminative stimulus effects in a dose-dependent manner and acts mainly on the α5 GABAA to produce the discriminative stimulus effect.
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http://dx.doi.org/10.1097/WNR.0000000000000959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851672PMC
March 2018

Integrated assessment and scenarios simulation of urban water security system in the southwest of China with system dynamics analysis.

Water Sci Technol 2017 Nov;76(9-10):2255-2267

Faculty of Environmental Engineering, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu 808-0135, Japan.

The demand for global freshwater is growing, while global freshwater available for human use is limited within a certain time and space. Its security has significant impacts on both the socio-economic system and ecological system. Recently, studies have focused on the urban water security system (UWSS) in terms of either water quantity or water quality. In this study, water resources, water environment, and water disaster issues in the UWSS were combined to establish an evaluation index system with system dynamics (SD) and geographic information systems (GIS). The GIS method performs qualitative analysis from the perspective of the spatial dimension; meanwhile, the SD method performs quantitative calculation about related water security problems from the perspective of the temporal dimension. We established a UWSS model for Guizhou province, China to analyze influencing factors, main driving factors, and system variation law, by using the SD method. We simulated the water security system from 2005 to 2025 under four scenarios (Guiyang scenario, Zunyi scenario, Bijie scenario and combined scenario). The results demonstrate that: (1) the severity of water security in cities is ranked as follows: three cities are secure in Guizhou province, four cities are in basic security and two cities are in a situation of insecurity from the spatial dimension of GIS through water security synthesis; and (2) the major driving factors of UWSS in Guizhou province include agricultural irrigation water demand, soil and water losses area, a ratio increase to the standard of water quality, and investment in environmental protection. A combined scenario is the best solution for UWSS by 2025 in Guizhou province under the four scenarios from the temporal dimension of SD. The results of this study provide a useful suggestion for the management of freshwater for the cities of Guizhou province in southwest China.
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http://dx.doi.org/10.2166/wst.2017.333DOI Listing
November 2017

Remission assessment of rheumatoid arthritis in daily practice in China: a cross-sectional observational study.

Clin Rheumatol 2018 Mar 7;37(3):597-605. Epub 2017 Nov 7.

The Hospital of Shunyi District Beijing, Shunyi District, China.

The objective of this study is to evaluate the remission rate and describe the current use of medication in a large cohort of rheumatoid arthritis (RA) patients under routine clinical care in China. RA patients were recruited from 40 large teaching hospitals nationwide in China. Data regarding RA disease activity, medication treatment, and adverse events were recorded using a standardized clinical data questionnaire. RA remission was evaluated by the 28 Joint Disease Activity Score DAS28-ESR Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria. A total of 1945 patients with RA were included in the study. The proportions of patients who fulfilled the DAS28-ESR, CDAI, SDAI, and ACR/EULAR remission criteria were 10.90%, 6.17%, 5.04% , and 1.75%, respectively. Most patients had taken at least one disease-modifying anti-rheumatic drug (DMARD), and the most common prescriptions included leflunomide (LEF) and methotrexate (MTX). DMARD combined with botanics were the most common and dominant strategy for RA management (29.16%). Overall, 433 patients (22.27%) had at least one adverse event. Gastrointestinal adverse events (41.27%) were the most frequently reported events. The incidence of side effects in patients using biologics DMARDs (bDMARDs) was significantly lower than that in those taking MTX, LEF, or sulfasalazine (SSZ). The remission rate of RA disease activity, as assessed in Chinese clinical practice, was very low. Adverse effects of the medicine occurred in approximately one in five RA patients, with bDMARDs were demonstrated to be the medication with the lowest side effects.
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http://dx.doi.org/10.1007/s10067-017-3850-zDOI Listing
March 2018

Heavy metal partitioning of suspended particulate matter-water and sediment-water in the Yangtze Estuary.

Chemosphere 2017 Oct 17;185:717-725. Epub 2017 Jul 17.

The Key Laboratory of Water and Sediment Sciences, Ministry of Education, School of Environment, Beijing Normal University, Beijing 100875, PR China.

The partitioning of ten heavy metals (As, Cd, Co, Cr, Cu, Hg, Ni, Pb, Sb, and Zn) between the water, suspended particulate matter (SPM), and sediments in seven channel sections during three hydrologic seasons in the Yangtze Estuary was comprehensively investigated. Special attention was paid to the role of tides, influential factors (concentrations of SPM and dissolved organic carbon, and particle size), and heavy metal speciation. The SPM-water and sediment-water partition coefficients (K) of the heavy metals exhibited similar changes along the channel sections, though the former were larger throughout the estuary. Because of the higher salinity, the K values of most of the metals were higher in the north branch than in the south branch. The K values of Cd, Co, and As generally decreased from the wet season to the dry season. Both the diagonal line method and paired samples t-test showed that no specific phase transfer of heavy metals existed during the flood and ebb tides, but the sediment-water K was more concentrated for the diagonal line method, owing to the relatively smaller tidal influences on the sediment. The partition coefficients (especially the K for SPM-water) had negative correlations with the dissolved organic carbon (DOC) but positive correlations were noted with the particle size for most of the heavy metals in sediment. Two types of significant correlations were observed between K and metal speciation (i.e., exchangeable, carbonate, reducible, organic, and residual fractions), which can be used to identify the dominant phase-partition mechanisms (e.g., adsorption or desorption) of heavy metals.
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http://dx.doi.org/10.1016/j.chemosphere.2017.07.075DOI Listing
October 2017

Impairment of Granzyme B-Producing Regulatory B Cells Correlates with Exacerbated Rheumatoid Arthritis.

Front Immunol 2017 30;8:768. Epub 2017 Jun 30.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.

Hyperactivated B cells have been demonstrated the contribution to the development of rheumatoid arthritis (RA). While the recognition of the negative regulatory function of B cells further promoted our understanding of their pathogenic role in RA. Recently, a new population of granzyme B (GrB)-producing B cells was identified, which was proved to be involved in cancer and infectious diseases. However, their characteristics and roles in RA remain to be elucidated. In the present study, we aim to further characterize whether B cells could produce GrB and reveal their potential role in the pathogenesis of RA. Here, we further demonstrated peripheral blood B cells from healthy individuals could produce and secrete GrB, which could be enhanced by IL-21 and/or anti-B-cell receptor stimulation. These cells could negatively regulate Th1 and Th17 cells partly downregulating TCR zeta chain and inducing T cell apoptosis, which might be termed as GrB-producing regulatory B cells (Bregs). These GrB-producing Bregs were significantly decreased under RA circumstance concomitant of lower levels of IL-21 receptor, with impaired regulatory functions on Th1 and Th17 cells. Moreover, the frequencies of these cells were negatively correlated with RA patient disease activity and clinical features. After effective therapy with disease remission in RA, these GrB-producing Bregs could be recovered. Therefore, our data revealed that B cells could produce GrB with immunosuppressive functions, and the impairment of this Breg subset was correlated with RA pathogenesis.
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http://dx.doi.org/10.3389/fimmu.2017.00768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491972PMC
June 2017

Cardiovascular disease in rheumatoid arthritis: medications and risk factors in China.

Clin Rheumatol 2017 May 24;36(5):1023-1029. Epub 2017 Mar 24.

Department of Rheumatology and Immunology, Hebei People's Hospital, 348 West Heping Rd, Shijiazhuang, 050051, China.

This study aims to assess the risk factors of cardiovascular disease (CVD) and to determine the association of traditional and biologic disease-modifying anti-rheumatic drugs (DMARDs) with risk for CVD in Chinese rheumatoid arthritis (RA) patients. A cross-sectional cohort of 2013 RA patients from 21 hospitals around China was established. Medical history of CVD was documented. The patients' social background, clinical manifestations, comorbidities, and medications were also collected. Of the 2013 patients, 256 had CVD with an incidence of 12.7%. Compared with non-CVD controls, RA patients with CVD had a significantly advanced age, long-standing median disease duration, more often male and more deformity joints. Patients with CVD also had higher rates of smoking, rheumatoid nodules, interstitial lung disease, and anemia. The prevalence of comorbidities, including hypothyroidism, diabetes mellitus (DM), hypertension, and hyperlipidemia, was also significant higher in the CVD group. In contrast, patients treated with methotrexate, hydroxychloroquine (HCQ), and TNF blockers had lower incidence of CVD. The multivariate analysis showed that the use of HCQ was a protective factor of CVD, while hypertension, hyperlipidemia, and interstitial lung disease were independent risk factors of CVD. Our study shows that the independent risk factors of CVD include hypertension, hyperlipidemia, and interstitial lung disease. HCQ reduces the risk of CVD in patients with RA.
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http://dx.doi.org/10.1007/s10067-017-3596-7DOI Listing
May 2017