Publications by authors named "Shiwen Yuan"

56 Publications

Effects of single-dose L-theanine on motor cortex excitability.

Clin Neurophysiol 2021 Sep 10;132(9):2062-2064. Epub 2021 Jul 10.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Butler Hospital, Providence, RI, USA.

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http://dx.doi.org/10.1016/j.clinph.2021.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384717PMC
September 2021

New Trends in Pharmacological Treatments for Osteoarthritis.

Front Pharmacol 2021 15;12:645842. Epub 2021 Apr 15.

Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.
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http://dx.doi.org/10.3389/fphar.2021.645842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085504PMC
April 2021

SSRI-Induced Hypersexuality.

Am J Psychiatry Resid J 2021 Mar 12;16(3):9-12. Epub 2021 Mar 12.

Drs. Yuan and Deban are fourth-year psychiatry residents in the Department of Human Behavior and Psychiatry, Brown University, Providence, R.I.

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http://dx.doi.org/10.1176/appi.ajp-rj.2021.160305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009557PMC
March 2021

NMDA-receptor agonist reveals LTP-like properties of 10-Hz rTMS in the human motor cortex.

Brain Stimul 2021 May-Jun;14(3):619-621. Epub 2021 Mar 29.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.

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http://dx.doi.org/10.1016/j.brs.2021.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164996PMC
March 2021

IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis.

Cell Mol Immunol 2021 Jul 11;18(7):1739-1750. Epub 2020 Sep 11.

Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong; Chongqing International Institute for Immunology, Hong Kong, China.

Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Currently, both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear. In this study, we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A (IL-17) stimulation in SLE patients and lupus mice. Using a humanized lupus mouse model, we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs. Moreover, long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU subsets among IL-17 receptor-expressing plasma cells. Lupus mice deficient in IL-17 or IL-17 receptor C (IL-17RC) exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage, while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice. In reconstituted chimeric mice, IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells. Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization. Together, our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis, which may provide new therapeutic strategies for the treatment of SLE.
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http://dx.doi.org/10.1038/s41423-020-00540-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245411PMC
July 2021

Flipped Classroom Approach Used in the Training of Mass Casualty Triage for Medical Undergraduate Students.

Disaster Med Public Health Prep 2020 Aug 7:1-8. Epub 2020 Aug 7.

Department of Emergency Medicine, the First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, China, 510080.

Objective: The aim of this study was to explore the application of the flipped classroom approach in the training of Mass Casualty Triage (MCT) to medical undergraduate students.

Methods: In this study, 103 fourth-year medical students were randomly divided into a Flipped Classroom (FC) group (n = 51) and a Traditional Lecture-based Classroom (TLC) group (n = 52). A post-class quiz, simulated field triage (SFT) and feedback questionnaires were performed to assess both groups of students for their learning of the course.

Results: In the post-quiz, the median (IQR) scores achieved by students from the FC and TLC groups were 42(5) and 39(5.5), respectively. Significant differences were found between the two groups. In the SFT, overall triage accuracy was 67.06% for FC, and 64.23% for TLC students. Over-triage and under-triage errors occurred in 18.43% and 14.50% of the FC group, respectively. The TLC group had a similar pattern of 20.77% over-triage and 15.0% under-triage errors. No significant differences were found regarding overall triage accuracy or triage errors between the two groups.

Conclusions: The FC approach could enhance course grades reflected in the post-quiz and improve students' satisfaction with the class. However, there was no significant difference of competency between the two groups demonstrated in the SFT exercise.
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http://dx.doi.org/10.1017/dmp.2020.162DOI Listing
August 2020

Acute pancreatitis concomitant with diabetic ketoacidosis: a cohort from South China.

J Int Med Res 2020 Mar;48(3):300060520912128

Department of Emergency Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

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http://dx.doi.org/10.1177/0300060520912128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132570PMC
March 2020

Attenuation of pristimerin on TNF-α-induced endothelial inflammation.

Int Immunopharmacol 2020 Mar 2;82:106326. Epub 2020 Mar 2.

Department of Digestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, ShenZhen, Guandong, China. Electronic address:

Objective: Pristimerin is known to have anti-cancer and anti-inflammatory activities; however, its therapeutic mechanism has not been described. In this study, to investigate the therapeutic mechanism of pristimerin, we examined the effect of pristimerin on TNF-α-induced endothelial inflammatory response both in vitro and in vivo.

Methods: Leukocyte-endothelium Adhesion Assay was use to evaluate the endothelial cell-monocyte interaction. Western blotting was used to confirm protein expression. NF-κB p65 nuclear translocation in endothelial cells was detected using immunofluorescent microscopy. In vivo leukocyte infiltration was evaluated using acute lung inflammation model.

Results: Pristimerin profoundly inhibited TNF-α-induced adhesion of monocytes to human endothelial cells and the leukocyte transmigration. Pristimerin dramatically inhibited the expression of TNF-α-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1)). Pristimerin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, pristimerin also suppressed the TNF-α-activated Nuclear factor kappa B (NF-κB) activation.

Conclusions: Pristimerin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of NF-κB activation, which may have a potential therapeutic effects for inflammatory vascular diseases.
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http://dx.doi.org/10.1016/j.intimp.2020.106326DOI Listing
March 2020

miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.

J Immunol Res 2019 1;2019:9827574. Epub 2019 Dec 1.

Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, No 1, Panfu Road, Guangzhou, China.

Objective: There is evidence that interleukin-6 (IL-6) upregulation plays a critical role in immunopathology of systemic lupus erythematosus (SLE). MicroRNA- (miRNA-) 98 was predicted to bind with the 3'-untranslated region (3'-UTR) of IL-6 gene. We hypothesized miR-98 through its regulation of IL-6 gene expression to influence cytokine production from peripheral blood mononuclear cells (PBMCs) in SLE.

Methods: The expression of miR-98 and IL-6 mRNA in the PBMCs of 41 SLE patients and 20 healthy controls (HC) was detected by quantitative reverse transcription PCR (qRT-PCR). The correlations between miR-98 expression and clinical features were evaluated. Luciferase reporter assay was performed to identify miR-98 targets. miR-98 mimics, miR-98 inhibitor, and IL-6 overexpression vector were generated. Cell viability of PBMCs was assessed using MTT assay. Gene expression and protein level were determined by qRT-PCR and Western blotting. TNF-, IL-8, IL-1, and IL-10 levels in cultured supernatants were quantified using ELISA.

Results: The expression of miR-98 was downregulated in PBMCs of SLE patients, and its expression is negatively associated with IL-6 levels. miR-98 expression was correlated with disease activity, lupus nephritis, and anti-dsDNA antibody. IL-6 mRNA was a target gene of miR-98. IL-6 overexpression promoted the proliferation of PBMCs and increased the levels of TNF-, IL-8, IL-1, and IL-10. Those effects were further enhanced by miR-98 inhibitor, while were suppressed by miR-98 mimics. miR-98 regulated the levels of STAT3 phosphorylation via its target gene IL-6.

Conclusion: The current study revealed that miR-98 could ameliorate STAT3-mediated cell proliferation and inflammatory cytokine production via its target gene IL-6 in patients with SLE. These results suggest that miR-98 might serve as a potential target for SLE treatment and other IL-6-mediated diseases.
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http://dx.doi.org/10.1155/2019/9827574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914974PMC
May 2020

Multiple Functions of B Cells in the Pathogenesis of Systemic Lupus Erythematosus.

Int J Mol Sci 2019 Nov 29;20(23). Epub 2019 Nov 29.

Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong 999077, China.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production and multi-organ involvement. Although the etiology of SLE still remains unclear, recent studies have characterized several pathogenic B cell subsets and regulatory B cell subsets involved in the pathogenesis of SLE. Among pathogenic B cell subsets, age-associated B cells (ABCs) are a newly identified subset of autoreactive B cells with T-bet-dependent transcriptional programs and unique functional features in SLE. Accumulation of T-bet CD11c ABCs has been observed in SLE patients and lupus mouse models. In addition, innate-like B cells with the autoreactive B cell receptor (BCR) expression and long-lived plasma cells with persistent autoantibody production contribute to the development of SLE. Moreover, several regulatory B cell subsets with immune suppressive functions have been identified, while the impaired inhibitory effects of regulatory B cells have been indicated in SLE. Thus, further elucidation on the functional features of B cell subsets will provide new insights in understanding lupus pathogenesis and lead to novel therapeutic interventions in the treatment of SLE.
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http://dx.doi.org/10.3390/ijms20236021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929160PMC
November 2019

Identification of Clinical Features and Biomarkers that may inform a Personalized Approach to rTMS for Depression.

Pers Med Psychiatry 2019 Nov-Dec;17-18:4-16. Epub 2019 Oct 18.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, 345 Blackstone Blvd., Providence, RI, 02906, USA.

Repetitive transcranial magnetic stimulation (rTMS), an established treatment for treatment-resistant depression, may hold promise as a personalized medicine approach for the treatment of major depressive disorder (MDD). Clinical research has begun to identify patient-specific factors that could be used to guide rTMS treatment decisions or individualized treatment approaches. This literature review describes a range of patient factors which have been evaluated as potential biomarkers of rTMS treatment response, including patient- and illness-related characteristics, genetic factors, and biomarkers derived from neuroimaging and EEG. We highlight the need for validation data for imaging and electrophysiological biomarkers associated with rTMS as well as prospective evaluation of clinical predictors. Finally, we consider implications for future efforts to move toward a personalized medicine approach in the treatment of depression with rTMS.
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http://dx.doi.org/10.1016/j.pmip.2019.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094130PMC
October 2019

Effect of Previous Electroconvulsive Therapy on Subsequent Response to Transcranial Magnetic Stimulation for Major Depressive Disorder.

Neuromodulation 2020 Apr 6;23(3):393-398. Epub 2019 Oct 6.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.

Objectives: Patients with major depressive disorder (MDD) who received electroconvulsive therapy (ECT) often seek transcranial magnetic stimulation (TMS) therapy as a less invasive treatment option. How prior history of ECT and its responsiveness may affect TMS treatment outcomes for MDD is unclear. We aim to contribute evidence to this important clinical question.

Materials And Methods: Retrospective naturalistic TMS treatment data from n = 257 MDD patients. Three sets of analyses were conducted: History of past exposure to ECT (n = 71, "+ECT" vs. n = 186 ECT-naïve, "-ECT") was examined as a potential predictor of TMS outcomes (measured by two self-report scales); A subset of n = 38 +ECT patients with adequate ECT trials in current depression episode were compared with -ECT patients blindly matched on clinical variables associated with TMS outcomes; for a subset with available data, TMS outcomes were explored in relation to positive/negative response to prior ECT.

Results: Compared to -ECT, +ECT patients more likely had past psychiatric hospitalizations (p < 0.01) and were more severely depressed at baseline (p = 0.07). Response (p = 0.07) and remission (p = 0.02) rates were higher in -ECT than +ECT groups on one scale. However, comparison between the subsets (n = 38 each) matched on confounding factors did not find history of ECT to be a significant independent predictor of TMS outcomes. Differential responsiveness to ECT and ECT treatment characteristics did not significantly impact TMS outcomes.

Conclusions: Although limited by the retrospective nature of this analysis, the results suggest that history of the past ECT, regardless of responsiveness to ECT, may not independently portend differential TMS treatment outcomes.
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http://dx.doi.org/10.1111/ner.13046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131879PMC
April 2020

Updates on Transcranial Magnetic Stimulation Therapy for Major Depressive Disorder.

Psychiatr Clin North Am 2018 09;41(3):419-431

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Box G-BH, Providence, RI 02912, USA; Butler Hospital, 345 Blackstone Boulevard, Providence, RI 02906, USA. Electronic address:

Transcranial magnetic stimulation has emerged as a treatment option for treatment-resistant depression. While existing data largely support efficacy of transcranial magnetic stimulation for major depressive disorder, ongoing research aims to optimize treatment parameters and identify biomarkers of treatment response. In this article, the authors describe data from controlled trials and ongoing efforts to enhance transcranial magnetic stimulation outcomes for major depressive disorder. Findings from preliminary research aimed at identifying neuroimaging and neurophysiological biomarkers of transcranial magnetic stimulation effects are discussed.
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http://dx.doi.org/10.1016/j.psc.2018.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979370PMC
September 2018

Clinical Trial of the Potassium Channel Activator Diazoxide for Major Depressive Disorder Halted Due to Intolerability.

J Clin Psychopharmacol 2018 Jun;38(3):243-246

Background: Some glutamatergic modulators have demonstrated rapid and relatively sustained antidepressant properties in patients with major depressive disorder. Because the potassium channel activator diazoxide increases glutamate uptake via potassium channel activation, we hypothesized that it might exert antidepressant effects by increasing the removal of glutamate from the synaptic cleft, thereby reducing excessive glutamate transmission.

Methods: This randomized, double-blind, placebo-controlled, crossover, single-site inpatient clinical study was conducted at the National Institute of Mental Health to assess the efficacy and safety of a 3-week course of diazoxide (200-400 mg daily, twice a day) versus a 3-week course of placebo in 6 participants with treatment-refractory major depressive disorder. The primary clinical outcome measure was change in Montgomery-Asberg Depression Rating Scale score from baseline to posttreatment. Quantitative insulin sensitivity check index, as well as concomitant imaging measures (electroencephalography, proton magnetic resonance spectroscopy, magnetoencephalography), were used as potential surrogate markers of target (KATP channel) engagement.

Results: The study was halted due to severe adverse effects. Given the small sample size, statistical evaluation of the effect of diazoxide on Montgomery-Asberg Depression Rating Scale scores or the imaging measures was not pursued. Visual inspection of the quantitative insulin sensitivity check index test revealed no evidence of target engagement.

Conclusions: Although the results are negative, they are an important addition to the literature in this rapidly changing field.
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http://dx.doi.org/10.1097/JCP.0000000000000866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903962PMC
June 2018

An automated method for identifying an independent component analysis-based language-related resting-state network in brain tumor subjects for surgical planning.

Sci Rep 2017 10 23;7(1):13769. Epub 2017 Oct 23.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

As a noninvasive and "task-free" technique, resting-state functional magnetic resonance imaging (rs-fMRI) has been gradually applied to pre-surgical functional mapping. Independent component analysis (ICA)-based mapping has shown advantage, as no a priori information is required. We developed an automated method for identifying language network in brain tumor subjects using ICA on rs-fMRI. In addition to standard processing strategies, we applied a discriminability-index-based component identification algorithm to identify language networks in three different groups. The results from the training group were validated in an independent group of healthy human subjects. For the testing group, ICA and seed-based correlation were separately computed and the detected language networks were assessed by intra-operative stimulation mapping to verify reliability of application in the clinical setting. Individualized language network mapping could be automatically achieved for all subjects from the two healthy groups except one (19/20, success rate = 95.0%). In the testing group (brain tumor patients), the sensitivity of the language mapping result was 60.9%, which increased to 87.0% (superior to that of conventional seed-based correlation [47.8%]) after extending to a radius of 1 cm. We established an automatic and practical component identification method for rs-fMRI-based pre-surgical mapping and successfully applied it to brain tumor patients.
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http://dx.doi.org/10.1038/s41598-017-14248-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653800PMC
October 2017

Long-term outcomes of the current remote magnetic catheter navigation technique for ablation of atrial fibrillation.

Scand Cardiovasc J 2017 Dec 28;51(6):308-315. Epub 2017 Sep 28.

a Section of Arrhythmias , Skåne University Hospital, Lund University , Lund , Sweden.

Objectives: Comparisons between remote magnetic (RMN) and manual catheter navigation for atrial fibrillation (AF) ablation have earlier been reported with controversial results. However, these reports were based on earlier generations of the RMN system.

Design: To evaluate the outcomes of the most current RMN system for AF ablation in a larger patient population with longer follow-up time, 112 patients with AF (78 paroxysmal, 34 persistent) who underwent AF ablation utilizing RMN (RMN group) were compared to 102 AF ablation patients (72 paroxysmal, 30 persistent) utilizing manual technique (Manual group).

Results: The RMN group was associated with significantly shorter fluoroscopy time (10.4 ± 6.4 vs. 16.3 ± 10.9 min, p < .001) but used more RF energy (64.1 ± 19.4KJ vs. 54.3 ± 24.1 KJ, p < .05), while total procedure time showed no significant difference (201 ± 35 vs. 196 ± 44 min, NS). After 39 ± 9/44 ± 10 months of follow-up, AF-free rates at 1year, 2 years and 3.5 years post ablation were 63%, 46% and 42% in the RMN group vs. 60%, 32% and 30% (survival analysis p < .05) in the Manual group, whereas clinically effective rates were 82%, 73% and 70% for the former vs. 70%, 56% and 49% for the latter (survival analysis p < .005).

Conclusion: Differing from previous reports, our data from a larger patient population and longer follow-up time demonstrates that compared to manual technique, the most current RMN technique is associated with better procedural and clinical outcomes for AF ablation.
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http://dx.doi.org/10.1080/14017431.2017.1384566DOI Listing
December 2017

The Role of Hippocampal Estradiol Receptor- in a Perimenopausal Affective Disorders-Like Rat Model and Attenuating of Anxiety by Electroacupuncture.

Evid Based Complement Alternat Med 2016 1;2016:4958312. Epub 2016 Dec 1.

Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Institutes of Brain Science, Brain Science Collaborative Innovation Center, Fudan University, Shanghai 200032, China.

Hormone replacement therapy is the principal treatment for perimenopausal affective disorders which can cause severe side effects. The present study compared the effects of electroacupuncture (EA) and estradiol treatment on perimenopausal affective disorders at the behavioral and cellular levels. In this randomized experimental study, adult female rats were divided into intact, ovariectomy, chronic unpredictable stress (CUS), and ovariectomy and CUS combination groups. After week 6, all groups were subdivided to three subgroups of control, EA, and estradiol treatment. The behavioral parameters in the open field and the elevated plus maze tests were assessed before and after treatments. Alterations of serum steroid hormones and changes of estradiol receptor- (ER-) immunofluorescence neurons in the hippocampus sections were evaluated. EA treatment caused more antianxiety effects than estradiol treatment in CUS group ( < 0.05). Notably, estradiol and EA treatments had better significant behavioral effects when the models were not estrogen-deficient. Importantly, within each group, compared to the control group, the numbers of ER--positive neurons were significantly larger in EA subgroups. Therefore, EA had antianxiety effects on perimenopausal affective disorders caused by CUS but not by estrogen deficiency and upregulation of hippocampus ER- neurons may contribute to its mechanism of action.
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http://dx.doi.org/10.1155/2016/4958312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156811PMC
December 2016

Prognostic value of lactate dehydrogenase in Chinese patients with newly diagnosed transplant eligible multiple myeloma.

Leuk Lymphoma 2017 07 23;58(7):1740-1742. Epub 2016 Nov 23.

a Department of Hematology , the First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.

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http://dx.doi.org/10.1080/10428194.2016.1252975DOI Listing
July 2017

Reduced response of IRE1α/Xbp-1 signaling pathway to bortezomib contributes to drug resistance in multiple myeloma cells.

Tumori 2017 May 7;103(3):261-267. Epub 2016 Sep 7.

Department of Hematology, First Affiliated Hospital of Sun Yat-Sen University, Guangdong - PR China.

Purpose: Proteasome inhibition with bortezomib eliminates multiple myeloma (MM) cells by partly disrupting unfolded protein response (UPR). However, the development of drug resistance limits its utility and resistance mechanism remains controversial. We aimed to investigate the role of IRE1α/Xbp-1 mediated branch of the UPR in bortezomib resistance.

Methods: The expression level of Xbp-1s was measured in 4 MM cell lines and correlated with sensitivity to bortezomib. LP1 and MY5 cells with different Xbp-1s level were treated with bortezomib; then pivotal UPR regulators were compared by immunoblotting. RPMI 8226 cells were transfected with plasmid pEX4-Xbp-1s and exposed to bortezomib; then apoptosis was determined by immunoblotting and flow cytometry. Bortezomib-resistant myeloma cells JJN3.BR were developed and the effect on UPR signaling pathway was determined.

Results: By analyzing 4 MM cell lines, we found little correlation between Xbp-1s basic level and bortezomib sensitivity. Bortezomib induced endoplasmic reticulum stress-initiated apoptosis via inhibiting IRE1α/Xbp-1 pathway regardless of Xbp-1s basic level. Exogenous Xbp-1s reduced cellular sensitivity to bortezomib, suggesting the change of Xbp-1s expression, not its basic level, is a potential marker of response to bortezomib in MM cells. Furthermore, sustained activation of IRE1α/Xbp-1 signaling pathway in JJN3.BR cells was identified.

Conclusions: Our data indicate that reduced response of IRE1α/Xbp-1 signaling pathway to bortezomib may contribute to drug resistance in myeloma cells.
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http://dx.doi.org/10.5301/tj.5000554DOI Listing
May 2017

Contribution of combined intraoperative electrophysiological investigation with 3-T intraoperative MRI for awake cerebral glioma surgery: comprehensive review of the clinical implications and radiological outcomes.

Neurosurg Focus 2016 Mar;40(3):E14

Glioma Surgery Division, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; and.

Objective: This study aimed to assess the clinical efficiency of combined awake craniotomy with 3-T intraoperative MRI (iMRI)-guided resection of gliomas adjacent to eloquent cortex performed at a single center. It also sought to explore the contribution of iMRI to surgeons' learning process of maximal safe resection of gliomas.

Methods: All patients who underwent an awake craniotomy and iMRI for resection of eloquent area glioma during the 53 months between January 2011 and June 2015 were included. The cases were analyzed for short- and long-term neurological outcome, progression-free survival (PFS), overall survival (OS), and extent of resection (EOR). The learning curve was assessed after dividing the cohort into Group A (first 27 months) and Group B (last 26 months). Statistical analyses included univariate logistic regression analysis on clinical and radiological variables. Kaplan-Meier and Cox regression models were used for further analysis of OS and PFS. A p value < 0.05 was considered statistically significant.

Results: One hundred six patients were included in the study. Over an average follow-up period of 24.8 months, short- and long-term worsening of the neurological function was noted in 48 (46.2%) and 9 (8.7%) cases, respectively. The median and mean EOR were 100% and 92%, respectively, and complete radiographic resection was achieved in 64 (60.4%) patients. The rate of gross-total resection (GTR) in the patients with low-grade glioma (89.06% ± 19.6%) was significantly lower than that in patients with high-grade glioma (96.4% ± 9.1%) (p = 0.026). Thirty (28.3%) patients underwent further resection after initial iMRI scanning, with a 10.1% increase of the mean EOR. Multivariate Cox proportional hazards modeling demonstrated that the final EOR was a significant predictor of PFS (HR 0.225, 95% CI 0.070-0.723, p = 0.012). For patients with high-grade glioma, the GTR (p = 0.033), the presence of short-term motor deficit (p = 0.027), and the WHO grade (p = 0.005) were independent prognostic factors of OS. Performing further resection after the iMRI (p = 0.083) and achieving GTR (p = 0.05) demonstrated a PFS benefit trend for the patients affected by a low-grade glioma. Over time, the rate of performing further resection after an iMRI decreased by 26.1% (p = 0.005). A nonsignificant decrease in the rate of short-term (p = 0.101) and long-term (p = 0.132) neurological deficits was equally noted.

Conclusions: Combined awake craniotomy and iMRI is a safe and efficient technique allowing maximal safe resection of eloquent area gliomas with possible subsequent OS and PFS benefits. Although there is a learning curve for applying this technique, it can also improve the surgeon's ability in eloquent glioma surgery.
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http://dx.doi.org/10.3171/2015.12.FOCUS15572DOI Listing
March 2016

Early-stage hip involvement in patients with ankylosing spondylitis: A Chinese study based on magnetic resonance imaging.

Mod Rheumatol 2016 Nov 4;26(6):933-939. Epub 2016 Mar 4.

a Department of Rheumatology , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China and.

Objectives: To evaluate the clinical characteristics and identify potential factors of the early-stage hip involvement in patients with ankylosing spondylitis (AS) based on the magnetic resonance imaging (MRI).

Methods: A cross-sectional retrospective study of 655 consecutive patients was performed. Patients with hip pain or limited hip function but lacking definitive evidence of hip involvement on radiography underwent hip MRI. Based on the results of the imaging tests, the patients were classified into three categories: (1) no hip involvement; (2) early-stage hip involvement according to MRI but not radiography; (3) advanced-stage hip involvement according to a Bath Ankylosing Spondylitis Radiology Index-hip score ≥2.

Results: One hundred and sixty-eight patients had early-stage hip involvement and 103 patients had advanced-stage hip involvement. Multivariate logistic regression analysis indicated that younger age at onset, worse BASMI score, and more active inflammation in the sacroiliac joints were associated with the occurrence of early-stage hip involvement.

Conclusion: Negative plain radiography results cannot be used to rule out hip involvement. MRI was superior to radiography for the detection of early-stage hip involvement. Susceptible AS patients with symptoms or risk factors for hip involvement should undergo hip MRI to test for lesions in the early stage.
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http://dx.doi.org/10.3109/14397595.2016.1153232DOI Listing
November 2016

Atrial average conduction velocity in patients with and without paroxysmal atrial fibrillation.

Clin Physiol Funct Imaging 2017 Nov 13;37(6):596-601. Epub 2016 Jan 13.

Section of Arrhythmias, Skåne University Hospital, Lund University, Lund, Sweden.

Objectives: To evaluate intra-atrial conduction delay in patients with atrial fibrillation (AF) via calculation of conduction velocities (CVs) of the right and left atria.

Methods: Electroanatomic mapping was performed during sinus rhythm, in the right atrium (RA) in eight patients with paroxysmal AF, in 12 controls with atrioventricular nodal re-entrant tachycardia (AVNRT) and in the left atrium (LA) in additional 16 AF patients. Three-dimensional maps of activation sequences of the RA and LA were obtained. Local CVs were specifically calculated in the direction of wave-front propagation on the activation maps by using 3-dimensional coordinates and local activation times of triads of sites. Average CVs of each atrium and each of 8 predefined RA and LA regions were calculated.

Results: During sinus rhythm, the average CVs of the RA were significantly slower (P<0·05) in the AF group (0·60 ± 0·12 m s ) than in the controls (0·83 ± 0·13 m s ). The average CVs of the RA basal, septal and annulus regions were significantly slower than the corresponding regions in controls (P<0·05). In patients with AF, the average CV of the LA was 0·51 ± 0·11 m s , which is significantly slower than that of the RA and than that of LA as previously reported (P<0·05).

Conclusion: Compared to patients with AVNRT, patients with AF are associated with conduction delay in both atria with the delay being more marked in the LA than in the RA, which suggests the involvement of conduction disturbances in the genesis and/or perpetuation of AF.
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http://dx.doi.org/10.1111/cpf.12342DOI Listing
November 2017

Factors Associated with Erosive Arthritis in Rheumatoid Arthritis and Other Connective Tissue Diseases: A Retrospective Study From a Southern Chinese Population.

J Clin Rheumatol 2016 Jan;22(1):22-9

From the *Department of Hematology, and †Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Objective: To investigate the clinical predictors of erosive arthritis (EA) in patients with rheumatoid arthritis (RA) and other connective tissue diseases.

Methods: Four hundred and one consecutive patients with newly diagnosed RA between January 2010 and January 2013 were enrolled in the study. During the study period, 729 consecutive patients with non-RA connective tissue diseases were also included, and a cross-sectional study was performed. Medical records were reviewed. Only those patients with data for 2 years were considered in the analysis (338).

Results: Erosive arthritis was noted in 60.4% (204 /338) of patients with RA and occurred early in RA. The multivariate logistic regression analysis indicated that rheumatoid nodules, anemia, and positive anticyclic citrullinated peptide antibody (ACPA) were strongly associated factors for the occurrence of EA in RA patients. Erosive arthritis was also noted in 1.5% of patients with SLE, 5.8% of patients with primary Sjögren syndrome, and 9.1% (3/33) of patients with systemic sclerosis. When compared with patients without EA, high level and prominently higher positive rate of ACPA was found in these patients with EA. On receiver operating characteristic curve analysis, ACPA exhibited a maximum sensitivity with a cutoff value of 1.6 U/mL and 0.6 U/mL for RA and SLE patients, respectively.

Conclusion: Erosive arthritis had a high prevalence in Chinese RA patients and occurred early. Anemia, rheumatoid nodules, and ACPA were associated with EA in RA. Erosive arthritis also could be detected in SLE, primary Sjögren syndrome, and systemic sclerosis. Anticyclic citrullinated peptide antibodies were also associated with EA in these diseases. Intensive monitoring for erosions was recommended for RA patients with a cutoff of ACPA greater than 1.6 U/mL and greater than 0.6 U/mL for SLE patients.
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http://dx.doi.org/10.1097/RHU.0000000000000341DOI Listing
January 2016

The effects of bromocriptine on preventing postpartum flare in systemic lupus erythematosus patients from South China.

J Immunol Res 2015 20;2015:316965. Epub 2015 Apr 20.

Department of Rheumatology & Clinical Immunology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.

Objective: Prolactin plays an important role on the disease flare of postpartum SLE patients. 76 pregnant SLE patients were enrolled in this study to evaluate the efficacy of bromocriptine (an inhibitor of prolactin secretion) on preventing the postpartum disease relapse.

Methods: Patients were randomly divided into the treatment group (bromocriptine, 2.5 mg oral, twice a day for 14 days after delivery) and the control group. All the patients were followed up for 12 months. Clinical features were recorded every 4 weeks. Serum prolactin and estradiol levels were measured at the second week and the second month after delivery. The endpoint of the study was disease relapse and defined when SLEDAI score increased by ≥3 points from the antenatal baseline.

Results: (1) Serum levels of prolactin and estradiol decreased significantly in bromocriptine treatment group at the second week (P < 0.001) and second month (P < 0.05) after delivery compared to control group. (2) The relapse rate of the treatment group was lower than the control group (χ (2) = 4.68, P = 0.0305).

Conclusions: Two weeks of oral bromocriptine treatment in postpartum SLE patients may relieve the disease from hyperprolactinemia and hyperestrogenemia and may be beneficial in preventing the patients from disease relapse.
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http://dx.doi.org/10.1155/2015/316965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418009PMC
February 2016

Incidence and predictive factors for malignancies with dermatomyositis: a cohort from southern China.

Clin Exp Rheumatol 2014 Sep-Oct;32(5):615-21. Epub 2014 Jul 28.

Department of Rheumatology and Clinical Immunology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Objectives: We aimed to explore the incidence of malignancy in dermatomyositis and assess the potential risk factors of occurrence of malignancy in DM from southern China.

Methods: A retrospective cohort study of patients admitted in the 1st affiliated university hospital between 2003 and 2012 was performed. Demographic information, clinical symptoms, laboratory findings, medications were documented. The endpoint of the study was defined as occurrence of malignancy or death.

Results: For this approximately 10-year retrospective study, 60 out of 246 dermatomyositis patients developed malignancies with the overall incidence of 24.4%. Nasopharyngeal carcinoma (NPC) and ovarian carcinoma were the most common malignant disease, accounting for 35% (21/60) and 15% (9/60) of malignancies, respectively. Lung and colon were followed as the third most common carcinoma (5 out of 60, 8.3%). Among these 60 patients with malignancies, 39 (65.0%, 39/60) cases occurred within 1 year after DM diagnosis. Subsequently, malignancies were detected in 13 (21.7%, 13/60) patients during the second year and 8 (13.3%, 8/60) during the third year. One patient developed cancer at the 35th month after DM as the latest. The logistic regression multivariate analysis indicated that male gender [odds ratio (OR) = 3.76, 95% confidence interval (CI ) 1.86~7.61, p<0.01], dysphagia (OR= 2.21, 95%CI 1.10~4.48, p=0.03) and elevated erythrocyte sedimentation rate (ESR) (OR= 2.37, 95% CI 1.18~4.75, p=0.02) were risk factors for the occurrence of malignancies, while interstitial lung disease (ILD) acted as a protective factor (OR=0.13, 95%CI 0.06~0.28, p<0.01).

Conclusions: It was necessary to carry out routine malignancy screening for Chinese DM patients due to its high incidence. Nasopharyngeal carcinoma and ovarian cancer were the most common malignant disease. The risk of malignancy was highest in the first year after DM diagnosis and reduced thereafter. Extensive work-ups for malignancy screening should be carried out at the first year. Male gender, dysphagia and elevated ESR were risk factors for occurrence of malignancy. The presence of ILD could diminish the risk of coexisting of malignancy.
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December 2014

[Assessment of ovarian reserve with anti-Müllerian hormone in female patients with systemic lupus erythematosus].

Zhonghua Yi Xue Za Zhi 2014 Apr;94(13):977-80

Email:

Objective: To evaluate the serum level of anti-Müllerian hormone (AMH) in female patients with systemic lupus erythematosus (SLE) and identify its correlations with age and cyclophosphamide (CYC) therapy.

Methods: A total of 77 SLE female patients and 38 control healthy women with regular menstrual cycles were recruited. AMH was measured by enzyme linked immunosorbent assay (ELISA) kit. Follicle-stimulating hormone (FSH), estradiol (E2) and antral follicle count (AFC) of bilateral ovary were detected at the third day of menstrual cycle.

Results: Their mean age was (29 ± 5) years (range, 20-40) and the mean duration (2.7 ± 2.4) years. The mean serum level of AMH was (1.5 ± 1.3) µg/L and AFC 10 ± 7. Linear regression revealed AFC (r = 0.9, P < 0.01) was associated with the level of AMH. The mean levels of AMH and AFC were significantly higher in patients naїve to CYC therapy than in those under exposure, but lower than that in healthy control (P < 0.01). No difference existed in FSH and E2 among 3 groups. Compared with those above 30 years old, the patients aged 30 years and younger had significantly higher level of AMH (P < 0.01). The Spearman's correlation analysis indicated that each 5 gm of CYC exposure were independently associated with a lower level of AMH (r = -0.4, P < 0.01).

Conclusion: As a more sensitive marker of ovarian reserve, AMH is associated with age and the cumulative dose of CYC. SLE patients aged >30 years and under exposure to CYC >10 g should be closely monitored for potential adverse events.
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April 2014

Coronary sinus cannulation with a steerable catheter during biventricular device implantation.

Scand Cardiovasc J 2014 Feb 27;48(1):41-6. Epub 2014 Jan 27.

Department of Arrhythmias, Skane University Hospital, Lund University , Lund , Sweden.

Objectives: To determine whether a steerable catheter with electrogram guidance (CS-assist group) could facilitate access to the coronary sinus (CS) during cardiac resynchronization therapy (CRT) implantation.

Design: Consecutive patients who underwent CRT implantation were recruited prospectively into the CS-assist group (n = 81) and compared with those using conventional techniques without an electrogram guidance (conventional group, n = 101).

Results: The CS cannulation success rate was clearly greater in the CS-assist group (100%) than that in the conventional group (95%, p < 0.05), with significantly shorter mean procedure time (52.6 ± 20.6 min vs. 73.2 ± 40.9 min, p < 0.01) and fluoroscopy time (3.6 ± 3.2 min vs. 14.2 ± 20.4 min, p < 0.01). In the five CS cannulation failure cases, mean procedure time (144.0 ± 37.0 min) and fluoroscopy time (57.8 ± 24.8 min) were significantly longer than those in the other patients (61.2 ± 32.3 and 8.2 ± 13.6 min, respectively, n = 177, both p < 0.01).

Conclusions: Using the steerable catheter with real-time electrogram guidance, location of and access to the CS is more rapid and successful, which may improve the success of the CRT implantation and may give significant time savings.
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http://dx.doi.org/10.3109/14017431.2013.875623DOI Listing
February 2014

Lupus mesenteric vasculitis: clinical features and associated factors for the recurrence and prognosis of disease.

Semin Arthritis Rheum 2014 Jun 12;43(6):759-66. Epub 2013 Nov 12.

Department of Rheumatology & Clinical Immunology, the First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Rd, Guangzhou 510080, China. Electronic address:

Objective: To evaluate the clinical characteristics of lupus mesenteric vasculitis (LMV) and identify the potential factors and appropriate treatments that are associated with disease relapse and prognosis in LMV.

Methods: A retrospective cohort study was performed among patients admitted to the First Affiliated Hospital of Sun Yet-sen University between 2002 and 2011. Demographic information, clinical symptoms, laboratory findings, imaging characteristics like abdominal CT scan, ultrasonography, medications including corticosteroid, cyclophosphamide, and other immunosuppressive agents, and outcomes were documented. The endpoints of the study were defined as occurrence of severe complications that needed surgical intervention, disease recurrence, or death.

Results: Out of 3823 systemic lupus erythematosus (SLE) patients, 97 were diagnosed with mesenteric vasculitis with the overall prevalence of 2.5%. Among these 97 LMV patients, 13 died because of serious complications (13/97, 13.4%) and 2 presented intestinal perforation during the induction therapy stage. The logistic regression multivariate analysis indicated that leukopenia [peripheral WBC, odds ratio (OR) = 0.640, 95% confidence interval (CI): 0.456-0.896, P = 0.009], hypoalbuminemia (serum albumin, OR = 0.891, 95% CI: 0.798-0.994, P = 0.039) and elevated serum amylase (OR = 7.719, 95% CI: 1.795-33.185, P = 0.006) were positively associated with the occurrence of serious complications, while intravenous cyclophosphamide (CYC) therapy inhibited the occurrence of serious complications (OR = 0.220, 95% CI: 0.053-0.903, P = 0.036). A total of 79 patients who achieved remission were followed-up for 2-96 months and 18 cases experienced disease relapse (18/79, 22.8%). The statistical analysis adjusted by Cox proportional hazards models indicated that high-dose CYC therapy (≥ 1.0 g/m(2)/month) was a protective factor for disease relapse and led to better outcomes [hazard ratio (HR) = 0.209, 95% CI: 0.049-0.887, P = 0.034], while the severe thickness of the bowel wall (>8mm) was a risk factor (HR = 7.308, 95% CI: 1.740-30.696, P = 0.007). LMV and lupus cystitis occurred concurrently in 22 (22/97, 22.7%) patients, and the symptoms of urinary tract resolved after treatment with corticosteroid and immunosupressants.

Conclusion: LMV is one of the serious complications of SLE with high mortality. The current study demonstrated that leukopenia, hypoalbuminemia, and elevated serum amylase were associated with severe adverse events, while CYC therapy led to better outcomes during remission-induction stage. Severe thickness of the bowel was a risk factor while high-dose CYC therapy was a protective factor for disease relapse in intensification therapy stage. It is necessary to evaluate the urinary tract involvement once LMV is diagnosed due to the frequent coexistence of these 2 diseases.
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http://dx.doi.org/10.1016/j.semarthrit.2013.11.005DOI Listing
June 2014

Association of thiopurine methyltransferase status with azathioprine side effects in Chinese patients with systemic lupus erythematosus.

Clin Rheumatol 2014 Apr 10;33(4):499-503. Epub 2013 Dec 10.

Department of Rheumatology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.

Azathioprine (AZA) is indicated for the treatment of systemic lupus erythematosus (SLE). Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in the steps of AZA metabolization. Heritable deficiency of TPMT enzyme activity and polymorphisms may lead to leukopenia. This study aims to detect TPMT polymorphisms and TPMT enzyme activity in Chinese SLE patients and to describe the association between TPMT genotypes and adverse effects of AZA. One hundred and twenty-six SLE patients with present or previous thiopurine therapy were identified from a local database. Adverse effects were documented. No TPMT*2, TPMT*3A, or TPMT*3B mutant alleles were detected. TPMT*3C was detected in four patients (3.17 %). The heterozygotes had significantly lower mean TPMT activity as compared to the homozygotes (2.38 ± 1.24 vs. 12.56 ± 7.02 U/mL, P < 0.001). Twenty-seven cases (21.42 %) exhibited adverse effects. All of the heterozygotes (4/4, 100 %) developed severe leukopenia, and three cases (3/4, 75 %) of whom exhibited alopecia simultaneously. The specificity of TPMT*3C for predicting leukopenia and alopecia was 100 and 99.17 %, respectively, and the sensitivity was 28.57 and 60.00 %, respectively. The mean value of TPMT activity with leukopenia (4.67 ± 3.01 vs. 13.2 ± 6.94 U/mL RBC, P < 0.001) or alopecia (2.31 ± 1.16 vs. 12.65 ± 6.98 U/mL RBC, P < 0.001) was significantly lower than those without. TPMT*3C was the most common mutant polymorphism found in the study group. TPMT activity is reduced in TPMT*3C mutant. AZA-induced leukopenia and alopecia were partly correlated to TPMT*3C heterozygotes and low TPMT activity. The results of this study suggest that the value of TPMT genotyping before AZA therapy was limited in Chinese SLE patients, considering the low sensitivity. Routine monitoring of TPMT activity before prescribing and continuous hematological monitoring dose were recommended.
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http://dx.doi.org/10.1007/s10067-013-2441-xDOI Listing
April 2014

Clinical features and associated factors of abdominal pain in systemic lupus erythematosus.

J Rheumatol 2013 Dec 1;40(12):2015-22. Epub 2013 Nov 1.

From the Department of Rheumatology and Clinical Immunology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Objective: To evaluate the clinical characteristics of systemic lupus erythematosus (SLE)-induced abdominal pain in a cohort in South China and identify the risk factors for SLE-induced abdominal pain.

Methods: This is a retrospective cohort study of SLE patients with complaint of abdominal pain admitted to the first affiliated university hospital of Sun Yat-sen University between 2002 and 2011. Demographic information, clinical features, laboratory findings, SLE Disease Activity Index, and imaging characteristics were documented.

Results: Of the 3823 SLE patients reviewed, 213 patients complained of abdominal pain and 132 cases were considered SLE-induced. The most common causes were lupus mesenteric vasculitis (LMV; 73.5%, 97/132) and lupus pancreatitis (LP; 17.4%, 23/132). Other causes included appendicitis, acute gastroenteritis, and peritonitis. Univariate and multivariate logistic regression analysis indicated the European Consensus Lupus Activity Measurement (ECLAM) score was significantly associated with lupus-induced abdominal pain (OR = 1.858, 95% CI: 1.441-2.394, p < 0.001), LMV (OR = 1.713, 95% CI: 1.308-2.244, p < 0.001), and LP (OR = 2.153, 95% CI: 1.282, 3.617, p = 0.004). The serum D-dimer level (OR = 1.004, 95% CI: 1.002-1.005, p < 0.001) was a strongly associated factor for lupus-induced abdominal pain. Moderate and large amounts of ascetic fluid was significantly associated with lupus-induced abdominal pain and LMV. Elevated liver enzymes was a risk factor for LP (OR = 34.605, 95% CI: 3.591-333.472, p = 0.002).

Conclusion: LMV and LP were the leading causes of SLE-induced abdominal pain. The serum D-dimer was a strongly associated factor for lupus-induced abdominal pain. ECLAM score was a reliable index in assessment of SLE-associated abdominal pain. Elevated liver enzymes, and moderate or large amounts of ascites, were positively associated with lupus-induced abdominal pain.
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http://dx.doi.org/10.3899/jrheum.130492DOI Listing
December 2013
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