Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors.

Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.

Polymorphisms in the ASAP1 and SP110 Genes and Its Association with the Susceptibility to Pulmonary Tuberculosis in a Mongolian Population.

Tuberculosis (TB) remains one of the deadliest infectious diseases in the world. Previous genome-wide association studies suggested that single-nucleotide polymorphisms (SNPs) in some genes could indicate the susceptibility to TB in some populations. Herein, we studied the association of SNPs in the immunity-related genes, i.e., ASAP1 and SP110 genes with the susceptibility to TB in a Mongolian population in China. A case-control study was performed with 197 TB patients and 217 healthy controls. Six SNPs in ASAP1 and six SNPs in SP110 were selected for genotyping test by second-generation sequencing technique. A SNP in SP110 gene (rs722555) was identified to be associated with susceptibility to TB in the Mongolian population (p < 0.05). The T allele of rs722555 in SP110 gene was associated with a 36% increase of risk at TB (OR 1.36, 95% CI 1.03-1.81), and the CT+TT genotype of rs722555 was associated with a 74% increase of risk at TB (OR 1.74, 95% CI 1.16-2.60) in the dominant genetic model. None of SNPs in ASAP1 gene tested in this study were significantly associated with TB susceptibility, while some individuals with SNPs (rs10956514, rs4733781, rs2033059, rs12680942, rs1017281, rs1469288, and rs17285138) in the ASAP1 gene tended to have a reduced risk at TB. In conclusion, this study suggested that the rs722555 SNP in SP110 gene might be a risk factor for TB in a Mongolian population.

Biomodal Tumor-Targeted and Redox-Responsive Bi2 Se3 Hollow Nanocubes for MSOT/CT Imaging Guided Synergistic Low-Temperature Photothermal Radiotherapy.

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, Bi2 Se3 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 Bi2 Se3 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 Bi2 Se3 HNC. This research designs a facile way to synthesize Bi2 Se3 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.

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

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.

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

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.

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

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.

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

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-1ß stimulated chondrocytes. ADMSCs decreased proinflammatory cytokines IL-1ß, IL-6, and TNF-α. ADMSCs enhanced the viability of IL-1ß 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-1ß 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.

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

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.

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

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.

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

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/m2 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.

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

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).

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

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, the presence of autoantibodies, regulatory T­cell 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 ConA­induced liver injury and a normal control. Blood samples were obtained to detect the levels of aminotransferases and inflammatory cytokines. Liver specimens were collected, and hematoxylin­eosin staining was used for histopathological examination and detection. Apoptosis was evaluated using the terminal deoxynucleotidyl-transferase­mediated dUTP nick end labeling (TUNEL) method. The expression levels of apoptosis­associated genes and proteins were determined by reverse transcription­quantitative 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 ConA­induced hepatitis. Increased levels of aminotransferases and inflammatory cytokines, including interferon­Î³, tumor necrosis factor­α, interleukin (IL)­4 and IL­2, were detected in ConA­treated 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 factor­related apoptosis­inducing ligand and caspase­3. Taken together, FXR activation ameliorated liver injury and suppressed inflammatory cytokines in ConA­induced hepatitis. FXR, therefore, exerts a protective role against ConA-induced apoptosis.

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

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.

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

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

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.

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

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.

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

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.

[Associated factors for the occurrence of lupus enteritis].

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.

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

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.

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

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.