Publications by authors named "Lian Fan"

45 Publications

Biomodal Tumor-Targeted and Redox-Responsive Bi Se Hollow Nanocubes for MSOT/CT Imaging Guided Synergistic Low-Temperature Photothermal Radiotherapy.

Adv Healthc Mater 2019 08 10;8(16):e1900250. Epub 2019 Jul 10.

Tianjin Key Laboratory of Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, P. R. China.

Hyperthemia (>50 °C) induced heating damage of nearby normal organs and inflammatory diseases are the main challenges for photothermal therapy (PTT) of cancers. To overcome this limitation, a redox-responsive biomodal tumor-targeted nanoplatform is synthesized, which can achieve multispectral optoacoustic tomography/X-ray computed tomography imaging-guided low-temperature photothermal-radio combined therapy (PTT RT). In this study, Bi Se hollow nanocubes (HNCs) are first fabricated based on a mild cation exchange way and Kirkendall effect and then modified with hyaluronic acid (HA) through redox-cleavable linkage (-s-s-), thus enabling the HNC to target cancer cells overexpressing CD-44 and control the cargo release profile. Finally, gambogic acid (GA), a type of heat-shock protein (HSP) inhibitor, which is vital to cells resisting heating-caused damage is loaded, into Bi Se HNC. Such HNC-s-s-HA/GA under a mild NIR laser irradiation can induce efficient cancer cell apoptosis, achieving PTT under relatively low temperature (≈43 °C) with remarkable cancer cell damage efficiency. Furthermore, enhanced radiotherapy (RT) can also be experienced without depth limitation based on RT sensitizer Bi Se HNC. This research designs a facile way to synthesize Bi Se HNC-s-s-HA/GA possessing theranostic functionality and cancer cells-specific GSH, but also shows a low-temperature PTT RT method to cure tumors in a minimally invasive and highly efficient way.
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http://dx.doi.org/10.1002/adhm.201900250DOI Listing
August 2019

Intra-arterial chemotherapy combined with intravesical chemotherapy is effective in preventing recurrence in non-muscle invasive bladder cancer.

J Cancer Res Clin Oncol 2019 Jun 21;145(6):1625-1633. Epub 2019 Mar 21.

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

Objective: To evaluate the efficacy and safety of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IC) in non-muscle invasive bladder cancer (NMIBC) and identify the risk factors for recurrence and progression.

Methods: This is a retrospective cohort study of NMIBC patients in south China. Ninety-nine patients underwent IAC combined with transurethral resection of bladder tumor (TURBT) and IC, and 50 patients underwent TURBT plus IC without IAC. The 5-year outcomes of the two groups were compared. Cox regression was used to evaluate risk factors. Kaplan-Meier curves were used to assess the significant differences of recurrence-free survival and progression-free survival.

Results: At 5 years, IAC significantly reduced the recurrence of high-grade NMIBC, 54.5% (18/33) in the non-IAC group vs 30.5% (18/59) in the IAC group (p = 0.028). IAC significantly reduced the recurrence of high-risk NMIBC, 56.3% (18/32) in the non-IAC group vs 26.1% (18/69) in the IAC group (p = 0.007). IAC significantly reduced the recurrence of intermediate-risk NMIBC, 44.4% (8/18) in the non-IAC group vs 22.2% (6/27) in the IAC group (p = 0.030). Tumors numbering from 2 to 7 had the highest recurrence rate (18.1%, 27/149). In this aspect, there was a significantly lower recurrence rate in the IAC group (30.8%, 12/30) than in the non-IAC group (68.2%, 15/22) (p = 0.007). No significant difference was found in the progression rate between the two groups. Only two cases (2/99, 2.0%) in the IAC group showed progression. The results of univariate and multivariate analyses suggested that the number of tumors, grade and risk level were risk factors for recurrence. No difference was found with respect to gender, age, tumor diameter, and T category. In the Kaplan-Meier plot, recurrence-free survival was significantly associated with treatment strategies (p < 0.01). Recurrence-free survival was shorter in the non-IAC group (12.73 ± 7.56 months) than in the IAC group (17.88 ± 12.26 months).

Conclusions: Combined IAC is a promising procedure to prevent recurrence and may be useful to suppress progression in NMIBC patients. The independent risk factors for the recurrence of NMIBC were multifocal tumors, grade and risk level. Intra-arterial chemotherapy is an effective and safe procedure and may be a promising choice in areas where BCG is not available or for patients who are intolerant to BCG.
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http://dx.doi.org/10.1007/s00432-019-02900-8DOI Listing
June 2019

Amplification of SMYD3 promotes tumorigenicity and intrahepatic metastasis of hepatocellular carcinoma via upregulation of CDK2 and MMP2.

Oncogene 2019 06 6;38(25):4948-4961. Epub 2019 Mar 6.

Department of Medical Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.

SMYD3, a member that belongs to the SET and MYND-domain (SMYD) family, has also been proven to largely participate in gene transcription regulation and progression of several human cancers as a histone lysine methyltransferase. However, the role and significance of SMYD3 in both the clinic and progression of hepatocellular carcinoma (HCC) remain unclear. Herein, we find that SMYD3 is increased in cirrhotic livers, and strikingly upregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Subsequent analyses suggest that high expression level of SMYD3 significantly correlates with the malignant characteristics of HCC, and predicts poor prognosis in patients. Our results show that overexpression of SMYD3 increases, while silencing of SMYD3 inhibits, cell proliferation, invasiveness and tumorigenicity both in vitro and in vivo. SMYD3 also promotes intrahepatic metastasis of HCC cells. For the mechanisms, we identify that SMYD3 bound to CDK2 and MMP2 promoter and increased H3K4me3 modification at the corresponding promoters to promote gene transcription. Importantly, pharmacological targeting of SMYD3 with BCI-121 inhibitor effectively repressed the tumorigenicity of HCC cells. Finally, our results show that gene locus amplification is a cause for SMYD3 overexpression in HCC. These findings not only uncover that SMYD3 overexpression promotes the tumorigenicity and intrahepatic metastasis of HCC cell via upregulation of CDK2 and MMP2, but also suggest SMYD3 could be a practical prognosis marker or therapeutic target against the disease.
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http://dx.doi.org/10.1038/s41388-019-0766-xDOI Listing
June 2019

Budd-Chiari syndrome in Behcet's disease: A report of two cases.

Exp Ther Med 2019 Mar 24;17(3):1737-1741. Epub 2018 Dec 24.

Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

Budd-Chiari syndrome (BCS) is a rare but severe venous form of Behcet's disease (BD) that is caused by the obstruction of the venous outflow tract that transports blood from hepatic veins into the inferior vena cava. In countries where BD is prevalent, including the Middle East and Far East, BCS awareness is important. In the present study, two cases of BCS are presented in two male Chinese patients with BD. The clinical characteristics, treatment and outcomes were recorded and compared with previous studies, and the features of BD-BCS were summarized. The clinical characteristics of the two patients documented were similar. Each patient presented with insidious onset, abdominal symptoms and recurrent aphthous ulcers. Accurate diagnosis was delayed as other symptoms of BD were overlooked. Each patient responded well to TNF-α inhibitor treatment in combination with cyclophosphamide (CYC). One patient with good compliance was removed from CYC and corticosteroid therapy. Unfortunately, the other patient with poor compliance faced a poor outcome. It was concluded that multiple vessel lesions in ≥2 sites are common in vasculo-BD and that misdiagnosis may occur if other symptoms of BD are not noticed. BD-BCS is associated with a high mortality rate, but appropriate treatment may result in a favorable outcome.
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http://dx.doi.org/10.3892/etm.2018.7130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364229PMC
March 2019

Formulation and durability of a geopolymer based on metakaolin/tannery sludge.

Waste Manag 2018 Sep 27;79:717-728. Epub 2018 Aug 27.

College of Environment, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

In this study, tannery sludge was used as a partial replacement material for a geopolymer. The best raw material composition of the geopolymer and durability of the solidified product were studied. Solidification effect was analyzed via compressive strength and total concentration of chromium leached. Its durability in terms of high-temperature resistance, acid/base resistance property, and resistance to acid rain erosion was studied. Through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Thermogravimetric Differential Thermal Analysis (TG-DTA) and scanning electron microscopy (SEM), the compressive strength and total concentration of chromium leached in different environments were analyzed. The results show that the mechanical properties of the solidified product were optimal when the silica/alumina mole ratio and sodium oxide/silica mole ratio were 2.45 and 0.37, respectively. The optimal raw material ratio of the above-mentioned product was used to synthesize a geopolymer containing 20% tannery sludge, with the solidified product showing high durability, as indicated by its good high-temperature resistance, high resistance to acids and alkalis, and great resistance to acid rain erosion.
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http://dx.doi.org/10.1016/j.wasman.2018.08.039DOI Listing
September 2018

Adipose derived mesenchymal stem cells alleviated osteoarthritis and chondrocyte apoptosis through autophagy inducing.

J Cell Biochem 2018 Oct 13. Epub 2018 Oct 13.

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

Objective: We aim to explore the effect of adipose derived mesenchymal stem cells (ADMSCs) on a knee osteoarthritis rat model and analyze how ADMSCs affect chondrocyte apoptosis.

Materials And Methods: A surgically induced rat knee osteoarthritis (OA) model was constructed. ADMSCs were engrafted into the right knee cavity. Hematoxylin and eosin (H&E), Masson, and Safranin O were used to compare the histopathology of synovial membrane and cartilage. Immunohistochemical (IHC) was used to measure MMP-13, Collagen 2 (Col-2), Caspase-3 (Cas-3), PARP, p62, LC3b, DDR-2, FGFR-1, Wnt, P-AKT/AKT, p-CAMKII/CAMKII, and p-Smad1/Smad1 expression in the articular cartilage. qPCR and Western blot analysis were used to detect mRNA and protein levels of markers in chondrocytes. TUNEL and Annexin-V were used to assess apoptosis.

Results: Histological analysis showed that ADMSCs alleviated the deterioration of cartilage and osteoarthritis. ADMSCs coculture increase the expression of Col2 and Sox-9, while down regulated MMP-13 in IL-1β stimulated chondrocytes. ADMSCs decreased proinflammatory cytokines IL-1β, IL-6, and TNF-α. ADMSCs enhanced the viability of IL-1β stimulated chondrocytes. ADMSC attenuated chondrocyte apoptosis. The pretreatment of 3-methyladenine (3-MA) reversed the reduction of Caspase-3 caused by ADMSCs, showing that the antiapoptotic effect was associated with autophagy inducing. ADMSCs significantly reduced the expression of FGFR-1, DDR-2, and Wnt in IL-1β stimulated chondrocytes. ADMSCs reduced the ratio of p-Smad1/Smad1 and p-CAMK II/CAMKII, and increased the ratio of p-AKT/AKT.

Conclusions: ADMSCs treatment alleviate osteoarthritis in rat OA models. AMDSCs reduced the secretion of proinflammatory cytokines and protected against apoptosis through autophagy inducing. ADMSCs' function could be related to multiple signaling pathway.
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http://dx.doi.org/10.1002/jcb.27530DOI Listing
October 2018

Efficiency of dose reduction strategy of etanercept in patients with axial spondyloarthritis.

Clin Exp Rheumatol 2018 Sep-Oct;36(5):884-890. Epub 2018 Apr 13.

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

Objectives: To evaluate the efficacy of different tapering or discontinuation strategies of etanercept in a cohort of axial spondyloarthritis from South China.

Methods: We performed a retrospective cohort study. Axial SpA patients who achieved clinical remission for at least 6 months after receiving a standard dose of etanercept therapy were enrolled. Different tapering or discontinuation strategies were compared.

Results: Altogether, 258 cases were enrolled. No differences were found in baseline characteristics among the three groups. Significantly more patients on discontinuation group (19%) than tapering group (5.4%, p<0.001) relapsed as early as 6 months. Almost all of the patients (103/107, 96.3%) in taper 25% group and more than 80% (71/88, 80.7%) of the patients in taper 50% group maintained low disease activity (LDA) or clinical remission during the first year. At the end of the 2-year follow-up, the percentage of patients maintaining LDA or remission were 28.6% (discontinuation), 55.7% (taper 50%), 84.1% (taper 25%), respectively. Activity indexes were significantly lower in taper 25% group compared to the other two groups. Patients in discontinuation group and tapering 50% group, with longer SpA duration were more likely to relapse, and remission>12 months before discontinuation/tapering helped to reduce relapse.

Conclusions: It is feasible to slowly increase the dosing interval and transit to the lowest effective dosing interval for some patients in remission/LDA. Prolonging the time under remission before tapering help to improve the outcome. Tapering 25% of the etanercept dose every 3 months may be a pragmatic approach for more cost-effective use of the drug.
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January 2019

Physical exercises and weight loss in obese patients help to improve uric acid.

Oncotarget 2017 Nov 25;8(55):94893-94899. Epub 2017 Oct 25.

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

Objective: to assess the impact of longitudinal change of the overweight and physical activity on hyperuricemia.

Methods: We performed a retrospective cohort study. Demographic information, clinical features, laboratory findings, body weight and physical exercises pattern were documented.

Results: Altogether 4678 cases of hyperuricemia were enrolled. The median aged males were most affected. Individuals in the middle age had the highest prevalence of being overweight (2501/3382, 74.0%). Middle aged with BMI≥25 kg/m were more likely to lose weight (963/2807, 34.3%). BMI and waist circumference control helped to reduce serum uric acid. Overweight population was more likely to use urate-lowering or uricosuric medication (3025/3382, 89.4%). Intermediate and heavy activity were associated with bigger SUA improvement. Patients in the age of 35-60 were more likely to do physical exercises than the others.

Conclusion: Being overweight is strongly associated with hyperuricemia. Successful weight control was correlated with significant uric acid reduction. Intermediate to heavy physical activity helps to reduce waist circumference and SUA. In the hyperuricemia population, obese, middle aged men were the most affected, and also the most likely to do more exercises and get their bodyweight back to normal.
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http://dx.doi.org/10.18632/oncotarget.22046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706921PMC
November 2017

Rare Cyclophosphamide-Induced Hemorrhagic Cystitis in a Chinese Population with Rheumatic Diseases.

Drugs Real World Outcomes 2017 Sep;4(3):175-182

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

Objective: The aim of this study was to investigate the prevalence, severity, risk factors, and treatment outcomes of cyclophosphamide (CYC)-induced hemorrhagic cystitis (HC) in patients with rheumatic diseases.

Methods: We collected the clinical data from 1284 consecutive patients admitted to The First Affiliated Hospital of Sun Yat-Sen University who were treated with CYC between 2006 and 2016, and then conducted a retrospective analysis.

Results: The mean cumulative dose of CYC was 18.3 ± 13.4 g, and the mean treatment duration of CYC was 10.0 ± 7.2 months. We identified four patients with HC, yielding a crude prevalence of 0.3%. The average time from initial primary diagnosis to HC onset was 51.6 months (33-86 months). All of the four patients with HC were exposed to a high cumulative CYC dose (>60 g). Severity was assessed as grade II in one, grade III in one and grade IV in two patients. One had resolution of hematuria after hydration, and one case resolved after combination therapy of clot removal by cystoscopy, hydration, and bladder irrigation. The other two were unresponsive to the above treatment and finally had resolution after cystectomy. The average resolution time of hematuria was 39.5 days (7-56 days). There were no deaths in our cohort.

Conclusion: CYC-induced HC was rare and highly variable in Chinese patients with rheumatic diseases. Individualized treatment should be performed according to the severity of HC for each patient. More aggressive treatment strategies might improve the outcomes of patients with high-grade HC (grades III and IV). Our findings strengthened the link between HC events and higher cumulative CYC exposure (>60 g).
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http://dx.doi.org/10.1007/s40801-017-0112-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567457PMC
September 2017

A Cationic Diode Based on Asymmetric Nafion Film Deposits.

ACS Appl Mater Interfaces 2017 Mar 16;9(12):11272-11278. Epub 2017 Mar 16.

Department of Chemistry, University of Bath , Claverton Down, Bath BA2 7AY, U.K.

A thin film of Nafion, of approximately 5 μm thickness, asymmetrically deposited onto a 6 μm thick film of poly(ethylene terephthalate) (PET) fabricated with a 5, 10, 20, or 40 μm microhole, is shown to exhibit prominent ionic diode behavior involving cation charge carrier ("cationic diode"). The phenomenon is characterized via voltammetric, chronoamperometric, and impedance methods. Phenomenologically, current rectification effects are comparable to those observed in nanocone devices where space-charge layer effects dominate. However, for microhole diodes a resistive, a limiting, and an overlimiting potential domain can be identified and concentration polarization in solution is shown to dominate in the closed state.
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http://dx.doi.org/10.1021/acsami.7b01774DOI Listing
March 2017

Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis.

Mol Med Rep 2015 Oct 31;12(4):5821-7. Epub 2015 Jul 31.

Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, the presence of autoantibodies, regulatory T‑cell dysfunction and raised plasma liver enzyme levels. The present study assessed the hepatoprotective and antiapoptotic role of farnesoid X receptor (FXR) in AIH. a mouse model of AIH was induced by treatment with concanavalin A (ConA). The FXR agonist, chenodeoxycholic acid (CDCA), was administered to mice exhibiting ConA‑induced liver injury and a normal control. Blood samples were obtained to detect the levels of aminotransferases and inflammatory cytokines. Liver specimens were collected, and hematoxylin‑eosin staining was used for histopathological examination and detection. Apoptosis was evaluated using the terminal deoxynucleotidyl-transferase‑mediated dUTP nick end labeling (TUNEL) method. The expression levels of apoptosis‑associated genes and proteins were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that FXR was downregulated at the mRNA and protein level in the liver specimens of mice induced with ConA‑induced hepatitis. Increased levels of aminotransferases and inflammatory cytokines, including interferon‑γ, tumor necrosis factor‑α, interleukin (IL)‑4 and IL‑2, were detected in ConA‑treated mice. The mice pretreated with the FXR agonist, CDCA, were more resistant to ConA hepatitis, as indicated by reduced levels of alanine transaminase/aspartate aminotransferase and aminotransferases. The activation of FXR ameliorated hepatocyte apoptosis, as demonstrated by TUNEL analysis and downregulation of the Fas/Fas ligand, tumor necrosis factor‑related apoptosis‑inducing ligand and caspase‑3. Taken together, FXR activation ameliorated liver injury and suppressed inflammatory cytokines in ConA‑induced hepatitis. FXR, therefore, exerts a protective role against ConA-induced apoptosis.
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http://dx.doi.org/10.3892/mmr.2015.4159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581797PMC
October 2015

Anti-TNFα agents and methotrexate in spondyloarthritis related uveitis in a Chinese population.

Clin Rheumatol 2015 Nov 13;34(11):1913-20. Epub 2015 Jun 13.

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

This study seeks to evaluate the clinical characteristics of spondyloarthritis (SpA)-related uveitis in a cohort from South China and to assess the efficacy and safety of therapies based on TNF blockers. SpA patients with uveitis admitted to a south China hospital were enrolled. Demographic information, clinical characteristics, laboratory findings, intraocular inflammation, visual acuity, macular thickness, and treatments were documented. Of the 1,036 SpA patients reviewed, 182 had uveitis. Ankylosing spondylitis (AS) was the most common subtype. Unilateral uveitis was found in 51 cases (51/182, 28.0%), and unilateral alternating uveitis was found in 75 cases (75/182, 41.2%). Half of the cases were recurrent uveitis (52.2%), and acute onset was common (76.4%). The most serious complication was vision loss (0.5%). No significant difference in disease activity was found between the SpA patients with or without uveitis. Predominant improvements were found in cases treated with all three anti-TNFs (infliximab, adalimumab, and etanercept) and anti-TNFs plus methotrexate (MTX). Monotherapy of methotrexate was not adequate for inducing remission. Monotherapy of etanercept was not as effective as adalimumab and infliximab, mainly in the prevention of recurrence. No significant difference in effectiveness was found among the three anti-TNFs if MTX was added. Etanercept plus MTX were well tolerated. Infliximab and adalimumab were associated with more tuberculosis and/or hepatitis flares. Uveitis is common in SpA patients. Severe complications may develop in prolonged and intractable cases. Treatments based on anti-TNFs had good clinical response, and better safety documentation were observed in etanercept plus MTX compared to the other two anti-TNF monoclonal antibodies plus MTX.
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http://dx.doi.org/10.1007/s10067-015-2989-8DOI Listing
November 2015

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

Comparative genomic analysis reveals multiple long terminal repeats, lineage-specific amplification, and frequent interelement recombination for Cassandra retrotransposon in pear (Pyrus bretschneideri Rehd.).

Genome Biol Evol 2014 Jun 4;6(6):1423-36. Epub 2014 Jun 4.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, College of Horticulture, Nanjing Agricultural University, China

Cassandra transposable elements belong to a specific group of terminal-repeat retrotransposons in miniature (TRIM). Although Cassandra TRIM elements have been found in almost all vascular plants, detailed investigations on the nature, abundance, amplification timeframe, and evolution have not been performed in an individual genome. We therefore conducted a comprehensive analysis of Cassandra retrotransposons using the newly sequenced pear genome along with four other Rosaceae species, including apple, peach, mei, and woodland strawberry. Our data reveal several interesting findings for this particular retrotransposon family: 1) A large number of the intact copies contain three, four, or five long terminal repeats (LTRs) (∼20% in pear); 2) intact copies and solo LTRs with or without target site duplications are both common (∼80% vs. 20%) in each genome; 3) the elements exhibit an overall unbiased distribution among the chromosomes; 4) the elements are most successfully amplified in pear (5,032 copies); and 5) the evolutionary relationships of these elements vary among different lineages, species, and evolutionary time. These results indicate that Cassandra retrotransposons contain more complex structures (elements with multiple LTRs) than what we have known previously, and that frequent interelement unequal recombination followed by transposition may play a critical role in shaping and reshaping host genomes. Thus this study provides insights into the property, propensity, and molecular mechanisms governing the formation and amplification of Cassandra retrotransposons, and enhances our understanding of the structural variation, evolutionary history, and transposition process of LTR retrotransposons in plants.
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http://dx.doi.org/10.1093/gbe/evu114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079214PMC
June 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

[Associated factors for the occurrence of lupus enteritis].

Zhonghua Yi Xue Za Zhi 2013 Apr;93(15):1162-4

Department of Rheumatology & Clinical Immunology, Affiliated First Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou 510080, China.

Objective: To explore the clinical and laboratory characteristics of patients with lupus enteritis to provide rationales for clinical diagnosis and treatment.

Methods: A retrospective group control study was conducted for systemic lupus erythematosus (SLE) patients with complaints of acute abdominal pain from 2004 to 2011. They were divided into 2 groups: lupus enteritis (n = 66) and non-lupus related abdominal pain (n = 73). The associated factors included demographic, laboratory, clinical and radiographic data.

Results: Lupus enteritis (39.3%) was the most common cause of lupus patients with acute abdominal pain. There were no differences in autoantibody profiles, complement, erythrocyte sedimentation rate, C reactive protein and SLE disease activity index (SLEDAI) score between two groups. The level of D-dimer and European consensus lupus activity measurement (ECLAM) score were significantly higher in the group of lupus enteritis than those in non-lupus related gastrointestinal injury. Lupus enteritis had significantly higher percentage of complications with multiple serous cavity effusions and ascites. But after adjusting with logistic regression multivariate analysis, only the level of D-dimer, ECLAM and volume of ascites were associated with occurrence of lupus enteritis.

Conclusion: Lupus enteritis is the most common cause of acute abdominal pain. D-dimer is an excellent predictor for lupus abdominal pain. As compared with SLEDAI, ECLAM may be more suitable for assessment in SLE patients with alimentary tract injury.
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April 2013

Clinical features and independent predictors in the further development of rheumatoid arthritis in undifferentiated arthritis.

Rheumatol Int 2013 Nov 9;33(11):2827-32. Epub 2013 Jul 9.

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

This study aims to investigate the prognosis of undifferentiated arthritis (UA) and to estimate the putative predictors contributing to predict the development of UA into rheumatoid arthritis (RA); thus, it could improve appropriate medical intervention. A retrospective cohort study of 218 patients with an initial diagnosis of UA and 2-year follow-up monitoring was carried out. The baseline information including demographic variables, clinical features, and laboratory data was collected. A logistic regression model was used for the statistical analysis. After 2 years of follow-up, 20.18% of UA patients evolved into RA, but 33.03% remained undifferentiated. Meanwhile, 25.23% went into remission, and 21.56% developed into other connective tissue diseases. Univariate and multivariate analysis showed that the titer of antibodies to cyclic citrullinated peptide (anti-CCP), tender joint count and duration of morning stiffness were independent predictors for the development of RA. The area under the curve (AUC) of duration of morning stiffness (0.81) was largest, followed by tender joint count (0.74). The AUC of anti-CCP antibodies (0.68) was higher than that of rheumatoid factor of IgM type (IgM-RF) (0.60), and the combination of these two antibodies was significantly higher than each alone (P < 0.001). In conclusion, UA patients had variable clinical outcomes and prognosis. Only the titer of anti-CCP antibodies, tender joint count, and duration of morning stiffness, instead of IgM-RF, could predict the development of RA. Although the anti-CCP antibody was better than the IgM-RF in predicting RA, a combined detection of them still improved the diagnostic performance.
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http://dx.doi.org/10.1007/s00296-013-2799-8DOI Listing
November 2013

Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats.

J Transl Med 2012 Jun 26;10:133. Epub 2012 Jun 26.

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

Introduction: Adipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4) in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway.

Methods: ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4)-induced liver fibrosis rats. Computed tomography (CT) perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated.

Results: CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII) immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF) was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein.

Conclusions: ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.
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http://dx.doi.org/10.1186/1479-5876-10-133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439354PMC
June 2012

[Spectrum of gene deletion in 471 children with α-thalassemia].

Zhongguo Dang Dai Er Ke Za Zhi 2012 Apr;14(4):264-6

Department of Pediatrics, Southern Medical University, Foshan, Guangdong, China.

Objective: To study the distribution of common α-thalassemia gene deletion in children.

Methods: Blood cell analysis was performed on children who visited the clinic of the Foshan Women and Children's Hospital. Blood samples (2 mL, EDTA anticoagulant) was collected from children with MCV<82 fl for analysis of α-thalassemia gene using the GAP-PCR method.

Results: MCV<82 fl was found in 1341 children. Of the 1341 children, 471 (35.1%) were diagnosed with α-thalassemia. The prevalence of α-thalassemia increased with increasing age. --SEA was a major type of α-thalassemia gene deletion (75.3%), followed by -a3.7 (17.0%) and -a4.2 (7.7%) in the 471 patients. The top three genotypes were --SEA/aa (73.2%), aa/-a3.7 (12.5%) and --SEA/-a3.7 (5.5%).

Conclusions: Genetic testing is necessary for the diagnosis of α-thalassemia in children with MCV<82 fl. --SEA is a common type of α-thalassemia gene deletion, and -SEA/aa is a common gene type of α-thalassemia in the subjects of this study.
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April 2012

Bile acids down-regulate caveolin-1 in esophageal epithelial cells through sterol responsive element-binding protein.

Mol Endocrinol 2012 May 3;26(5):819-32. Epub 2012 Apr 3.

Department of Chemistry, Klinikum rechts der Isar, Technische Universität München, D-81675 Munich, Germany.

Bile acids are synthesized from cholesterol and are major risk factors for Barrett adenocarcinoma (BAC) of the esophagus. Caveolin-1 (Cav1), a scaffold protein of membrane caveolae, is transcriptionally regulated by cholesterol via sterol-responsive element-binding protein-1 (SREBP1). Cav1 protects squamous epithelia by controlling cell growth and stabilizing cell junctions and matrix adhesion. Cav1 is frequently down-regulated in human cancers; however, the molecular mechanisms that lead to this event are unknown. We show that the basal layer of the nonneoplastic human esophageal squamous epithelium expressed Cav1 mainly at intercellular junctions. In contrast, Cav1 was lost in 95% of tissue specimens from BAC patients (n = 100). A strong cytoplasmic expression of Cav1 correlated with poor survival in a small subgroup (n = 5) of BAC patients, and stable expression of an oncogenic Cav1 variant (Cav1-P132L) in the human BAC cell line OE19 promoted proliferation. Cav1 was also detectable in immortalized human squamous epithelial, Barrett esophagus (CPC), and squamous cell carcinoma cells (OE21), but was low in BAC cell lines (OE19, OE33). Mechanistically, bile acids down-regulated Cav1 expression by inhibition of the proteolytic cleavage of 125-kDa pre-SREBP1 from the endoplasmic reticulum/Golgi apparatus and nuclear translocation of active 68-kDa SREBP1. This block in SREBP1's posttranslational processing impaired transcriptional activation of SREBP1 response elements in the proximal human Cav1 promoter. Cav1 was also down-regulated in esophagi from C57BL/6 mice on a diet enriched with 1% (wt/wt) chenodeoxycholic acid. Mice deficient for Cav1 or the nuclear bile acid receptor farnesoid X receptor showed hyperplasia and hyperkeratosis of the basal cell layer of esophageal epithelia, respectively. These data indicate that bile acid-mediated down-regulation of Cav1 marks early changes in the squamous epithelium, which may contribute to onset of Barrett esophagus metaplasia and progression to BAC.
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http://dx.doi.org/10.1210/me.2011-1140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417097PMC
May 2012

Inhibitory effects of simvastatin on migration and invasion of rheumatoid fibroblast-like synoviocytes by preventing geranylgeranylation of RhoA.

Rheumatol Int 2013 Feb 27;33(2):389-99. Epub 2012 Mar 27.

Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, Guangdong, People's Republic of China.

To investigate the effect of simvastatin on the migration and invasion of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and its cellular signal mechanisms, FLS from active RA patients were stimulated with 3 % FBS or GM-CSF in the presence or absence of simvastatin. Cells migration and invasion in vitro were measured by the Boyden chamber method. RhoA activity was assessed by a pull-down assay. Matrix metalloproteinases-2 (MMP-2) activity was evaluated by zymography. Simvastatin inhibits FBS- or GM-CSF-induced migration in a dose-dependent manner by RA FLS, and this inhibitory effect is independent of cell apoptosis. We also found that simvastatin suppressed in vitro invasion, adhesion, MMP-2 activity, cytoskeletal reorganization and RhoA activation. Furthermore, mevalonate or GGPP treatment reversed the inhibitory effect of simvastatin not only on migration and invasion in vitro but also on RhoA activation, and inhibition of RhoA by specific siRNA transfection reduced migration, adhesion and invasion of RA FLS. This study shows that simvastatin reduces RA FLS migration and invasion through the prevention of protein geranylgeranylation and RhoA activation. These findings provide a novel evidence that statin may be benefit for preventing RA arthritic destruction, and also indicate that RhoA may be a new target for the modulation of RA FLS migration and invasion.
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http://dx.doi.org/10.1007/s00296-012-2383-7DOI Listing
February 2013

Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage.

Biochem J 2011 Sep;438(2):315-23

Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Bile acids from duodenogastric reflux promote inflammation and increase the risk for gastro-oesophageal cancers. FXR (farnesoid X receptor/NR1H4) is a transcription factor regulated by bile acids such as CDCA (chenodeoxycholic acid). FXR protects the liver and the intestinal tract against bile acid overload; however, a functional role for FXR in the stomach has not been described. We detected FXR expression in the normal human stomach and in GC (gastric cancer). FXR mRNA and protein were also present in the human GC cell lines MKN45 and SNU5, but not in the AGS cell line. Transfection of FXR into AGS cells protected against TNFα (tumour necrosis factor α)-induced cell damage. We identified K13 (keratin 13), an anti-apoptotic protein of desmosomes, as a novel CDCA-regulated FXR-target gene. FXR bound to a conserved regulatory element in the proximal human K13 promoter. Gastric expression of K13 mRNA was increased in an FXR-dependent manner by a chow diet enriched with 1% (w/w) CDCA and by indomethacin (35 mg/kg of body weight intraperitoneal) in C57BL/6 mice. FXR-deficient mice were more susceptible to indomethacin-induced gastric ulceration than their WT (wild-type) littermates. These results suggest that FXR increases the resistance of human and murine gastric epithelial cells to inflammation-mediated damage and may thus participate in the development of GC.
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http://dx.doi.org/10.1042/BJ20102096DOI Listing
September 2011

[Radiological progression and life quality analysis in ankylosing spondylitis patients using etanercept/methotrexate combination therapy].

Zhonghua Yi Xue Za Zhi 2011 Apr;91(15):1022-5

Department of Interventional Radiology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.

Objective: To analyze the relationship between the radiological progression and quality of life in ankylosing spondylitis (AS) patients using etanercept/methotrexate (MTX) combination therapy.

Methods: A total of 153 AS cases fulfilling the 1984 modified New York diagnostic criteria were reviewed. All patients received radiological evolution at baseline and during a follow-up period. Radiological progression, clinical remission and life quality were recorded and analyzed for their relations.

Results: The radiological assessments of mSASSS (modified Stoke ankylosing spondylitis spine score) were recorded at baseline, 3, 6 & 12 months after treatment. Life quality assessments were recorded with SF (short-form)-36 simultaneously. No significant radiological improvement was observed at the end points. However, most patients reported a significant improvement of life quality after a combination therapy of etanercept/MTX. BASDAI (Bath ankylosing spondylitis disease activity index), C-reactive protein and erythrocyte sedimentation rate demonstrated similar trends. With no relevance with mSASSS, life quality was significantly correlated with disease activity and pain control.

Conclusion: The combination therapy of etanercept/MTX greatly improves life quality in AS patients. Yet clinical remission and pain control offer no hint of a suspension of radiological progression. Routine radiological assessment is required throughout the follow-up period of AS even if life quality index reaches a high level.
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April 2011

Clinical features and independent predictors of pulmonary arterial hypertension in systemic lupus erythematosus.

Rheumatol Int 2012 Jun 25;32(6):1727-31. Epub 2011 Mar 25.

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

Pulmonary arterial hypertension (PAH) is a devastating complication of systemic lupus erythematosus (SLE). We aim to estimate the putative predictors contributing to early identification of PAH, thus improve appropriate medical intervention and a better prognosis. A retrospective case-control study was conducted. Forty-one SLE patients with PAH and 106 SLE patients without PAH were enrolled. Demographic variables, clinical features, and laboratory data were compared between the two groups. Univariate and multivariate logistic regression models were used to examine the predictors contributing to PAH in SLE. Serositis, Raynaud's phenomenon, high disease activity, anticardiolipin antibodies, and anti-U1RNP were significantly associated with SLE-PAH. Univariate and multivariate analysis showed that Raynaud's phenomenon, anticardiolipin antibodies, and anti-U1RNP were independent predictors of PAH in SLE. This study highlighted the clinical pattern of SLE-PAH patients, and underlined the leading predictors of PAH development among patients with SLE. Routine echocardiography is recommended in SLE patients with the independent predictors mentioned above.
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http://dx.doi.org/10.1007/s00296-011-1880-4DOI Listing
June 2012

Activation of farnesoid X receptor attenuates liver injury in systemic lupus erythematosus.

Rheumatol Int 2012 Jun 24;32(6):1705-10. Epub 2011 Mar 24.

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

To investigate the expression and effect of farnesoid X receptor (FXR) on systemic lupus erythematosus (SLE) liver dysfunction and indicate its hepatoprotective role and the immunomodulatory property. mRNA and protein levels of FXR were determined on the liver specimens of SLE patients with liver injury as well as MRL/lpr rodent models. The FXR agonist chenodeoxycholic acid (CDCA) was administrated to MRL/lpr mice and the control BALB/C with concanavalin A (ConA)-induced liver injury. Blood samples were taken 0, 4, 8, 12, 16, and 24 h after ConA injection for the detection of serum ALT, AST, IFN-γ, TNF-α, and IL-6. FXR was down-regulated at both mRNA and protein levels in the liver specimens of SLE patients with liver injury as well as MRL/lpr mice. MRL/lpr was more susceptible to ConA than BALB/C indicated by significantly higher levels of aminotransferase and inflammatory cytokines. Activation of FXR by CDCA significantly reduced aminotransferase and inflammatory cytokines IFN-γ, TNF-α, and IL-6 caused by ConA injection in MRL/lpr mice. FXR was down-regulated in SLE patients as well as MRL/lpr lupus models with liver dysfunction. FXR activation ameliorated liver injury and suppressed inflammatory cytokines, thereby showing its protective function in SLE. Our findings raised the promising potential target for the treatment of SLE liver injury.
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http://dx.doi.org/10.1007/s00296-011-1874-2DOI Listing
June 2012

Treatment efficacy of etanercept and MTX combination therapy for ankylosing spondylitis hip joint lesion in Chinese population.

Rheumatol Int 2012 Jun 9;32(6):1663-7. Epub 2011 Mar 9.

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

To investigate the efficacy of etanercept and MTX (methotrexate) combination therapy in Chinese patients with ankylosing spondylitis hip joint lesion, the possible courses and maintenance protocol, altogether 97 ankylosing spondylitis patients fulfilling the modified New York criteria with hip joint lesion were enrolled in a 12-month trial treated with combined etanercept and MTX. All these patients were required to be poor responders to SSZ (Sulfasalazine) or MTX therapy for 6 consecutive months or the longer. Etanercept was administered subcutaneously twice a week at a fixed dosage of 25 mg for the first six months, followed by 25 mg once a week in patients with good control of both symptoms and radiological progression, or twice a week for another six months in patients with BASDAI > or = 4. Combined MTX was administered intravenously once a week at the dosage of 15 mg. Demographics, clinical and laboratory features, physical function and quality of life using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), Harris hip score, and radiological assessment using the BASRI-hip index were recorded. Most patients achieved pain release at the end point of assessment. Significant improvement in Bath AS Disease Activity Index (BASDAI) (P < 0.05), Bath AS Functional Activity Index (BASFI) (P < 0.05), and Harris hip score (P < 0.05) was demonstrated. Radiographic progression was recorded as no exacerbation or alleviated. Larger interval between two etanercept administrations would provide similar advantages to standard method and possibly less adverse events if MTX was combined. Etanercept and MTX combination therapy was beneficial to ankylosing spondylitis patients with hip joint lesion, and staged dosage deduction in the long term proved to be effective as well as adverse event preventing.
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http://dx.doi.org/10.1007/s00296-011-1844-8DOI Listing
June 2012

[Clinical analysis of 6 cases of systemic lupus erythematosus complicated by transverse myelitis].

Nan Fang Yi Ke Da Xue Xue Bao 2011 Feb;31(2):313-6

Fifth Department of Internal Medicine, Huiyang People's Hospital, Huizhou 516211, China.

Objective: To summarize the clinical features and therapeutic approach of systemic lupus erythematosus (SLE) complicated by transverse myelitis (TM).

Methods: The clinical characteristics, laboratory examinations, treatment and prognosis of 6 SLE cases with TM were retrospectively analyzed with review of the literatures.

Results: The 6 patients consisted of 5 females and 1 male aged 14 to 36 years (mean 23 years). The mean duration from symptom onset of SLE to TM was 8 months (1 to 13 months). All the patients had lower limb hypodynamia, and 3 of them developed upper limb hypodynamia. MRI scanning of the spine identified lesions in the cervical spinal cord in 2 cases, thoracic lesions in 3 cases, and multiple involvement of the cervical, thoracic and lumbar cord in 1 case. Examination of the cerebrospinal fluid yielded no specific findings except for leukocytosis in 1 case and hypoglycemia in another. Five cases were treated with high-dose MP+CTX, and the other case was treated with MP (80 mg/day)+CTX. Five patients responded favorably to the treatment, while the other showed no obvious improvement.

Conclusion: TM is a rare complication of SLE affecting mostly young patients and occurring in the early stage of the disease. Early diagnosis and aggressive treatment might improve the prognosis.
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February 2011
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