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1.
Inflammation ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125593

RESUMO

Although the E3 ubiquitin ligase Zinc and ring finger 3 (ZNRF3) negatively regulates the Wnt signaling pathway, its function in rheumatoid arthritis (RA) is elusive. Here, the effects and the mechanism of ZNRF3 on a mouse model of collagen-induced arthritis (CIA) and human fibroblast-like synoviocytes (FLS) obtained from RA patients were determined. Our results showed that ZNRF3 was highly expressed in tissues and FLSs compared to trauma patients. Lentivirus-mediated silencing of ZNRF3 induced apoptosis decreased cell viability and significantly attenuated inflammation in RA-FLSs via tumor necrosis-α (TNF-α). Additionally, silencing of ZNRF3 reduced knee joint damage and also decreased the level of TNF-α, IL-1ß, and IL-6 in the CIA mouse model. These effects were mediated by the crosstalk between Wnt and NF-κB pathways in RA-FLS.

2.
Lipids Health Dis ; 19(1): 36, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164741

RESUMO

BACKGROUND: Systemic inflammation may be involved in the formation and progression of thyroid nodule (TN). The aim of this large-scale study was to investigate the association of several simple inflammatory markers with the presence and size of TN. METHODS: A total of 133,698 adults were included for the current analysis. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and monocyte-to-high-density lipoprotein cholesterol ratio (MHR) were calculated. The logistic regression was used to explore the association of the four markers with the presence and size of TN. RESULTS: The prevalence of TN was 55.1% among females and 44% among males; 13% of women and 8% of men had non-micronodule. In women, MHR and PLR were significantly associated with the presence of TN and non-micronodule; in men, MHR and NLR were significantly associated with the presence of TN and non-micronodule. CONCLUSIONS: As a low-cost, simple, and reproducible inflammatory marker, MHR is strongly associated with the presence and size of TN irrespective of the gender.

3.
Clin Exp Rheumatol ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31820727

RESUMO

OBJECTIVES: Aneurysm formation can cause life-threatening complications in Takayasu's arteritis (TAK). The objective of this study was to evaluate the demographic, clinical and angiographic features, and outcomes of aneurysm secondary to TAK in Chinese patients. METHODS: The medical charts of patients diagnosed with TAK in Changhai Hospital between 2001 and 2017 were retrospectively reviewed. RESULTS: Aneurysms were identified in 66 (16.6%) of 397 patients with TAK. The mean age at onset was 30.4±11.5 years, with a male:female ratio of 1:2.7. Patients with aneurysm had a higher proportion of male (p<0.01), higher incidences of bruit, chest tightness and aortic regurgitation (all p<0.001), and a lower incidence of visual disturbances (p<0.01) as compared with patients without aneurysm. The prevalence of elevated ESR and CRP and ITAS2010 score were higher in patients with than without aneurysm (all p<0.01). Angiographic classification showed that type V (30.3%) was the most frequent pattern in patients with aneurysm though Type I was dominant in patients without aneurysm. Multiple aneurysms were found in 30.3% of patients and the most common site of aneurysms was abdominal aorta (22.1%). Glucocorticoids were prescribed in 86.4% of patients with aneurysm, and surgical procedures were performed in 80.3%. Five of 52 patients died during the median 3-year follow-up period. CONCLUSIONS: These findings could provide useful information on the demographical, clinical and angiographic features of TAK patients with aneurysm. Aneurysm formation in TAK may be associated with male gender and active vascular inflammation.

4.
Chin Med J (Engl) ; 132(24): 2899-2904, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31855969

RESUMO

BACKGROUND: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development. METHODS: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression. RESULTS: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001). CONCLUSION: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

5.
Clin Rheumatol ; 38(11): 3227-3233, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31300980

RESUMO

OBJECTIVE: The association between hyperuricemia and insulin resistance (IR) has been demonstrated by many studies, but the traditional IR indexes are too impractical to be used in clinical practice for the recognition of the IR state in individuals with hyperuricemia. Therefore, we aimed to further investigate the association between hyperuricemia and three non-insulin-based IR indexes in this large-scale cross-sectional study. METHODS: A total of 174,695 adults without self-reported use of antihyperuricemic agents, hypoglycemic agents, or lipid-lowering drugs were included in the current analysis. The triglyceride to high-density lipoprotein cholesterol ratio (TG/HDLc), the product of fasting triglycerides and glucose (TyG), and metabolic score for IR (METS-IR) were calculated. Then, logistic regression analyses were applied to explore their association with hyperuricemia. RESULTS: The TG/HDLc, TyG, and METS-IR all had positive correlations with uric acid level. However, only TG/HDLc and TyG were significantly associated with hyperuricemia in both sexes and body mass index (BMI) classification (the ORs of the highest quartile for each were 6.751 and 1.505 in females and 6.487 and 1.646 in males, respectively). The AUC values of TG/HDLc and TyG to discriminate hyperuricemia were also statistically significant in both sexes and BMI classification (all greater than 0.7). CONCLUSIONS: TG/HDLc and TyG are strongly associated with hyperuricemia regardless of BMI classification. These two obtainable and cost-effective non-insulin-based IR indexes could be potential monitors during the management of hyperuricemia and prevention of its IR-driven comorbidities. Key Points • In this large-scale study, we identified TG/HDLc and TyG as indicators for identification of IR in patients with hyperuricemia. • These simple and practical IR indicators are of substantial clinical importance for implementing preventive strategies against IR-driven comorbidities of hyperuricemia.

6.
J Cell Physiol ; 234(10): 17663-17676, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30912120

RESUMO

Synovial fibroblasts (SFs) of rheumatoid arthritis (RA) are phenotypically aggressive, typically progressing into arthritic cartilage degradation. Throughout our study, we made explorations into the effects of microRNA-135a (miR-135a) on the SFs involved in RA by mediating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway via regulation of phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2). The expression of PI3K was higher, the expression of PIK3R2 was lower, and AKT was phosphorylated in the RA synovial tissues, relative to the levels found in the normal synovial tissues. We predicted miR-135a to be a candidate miR targeting PIK3R2 using an online website, microRNA.org, which was verified with a dual-luciferase reporter gene assay. Subsequently, high miR-135a expression was observed in RA synovial tissues. To study the effect of the interaction between miR-135a and PIK3R2 in RA, the SFs isolated from RA samples were cultured and transfected with mimic, inhibitor, and small interfering RNA. The proliferation, invasion, and apoptosis of the SFs were detected after the transfection. The cells transfected with miR-135a inhibitor showed inhibited cell proliferation, migration, and invasion, while also displaying promoted cell apoptosis, G0/G1 cell ratio, and decreased S cell ratio, through upregulation of PIK3R2 and inactivation of the PI3K/AKT signaling pathway. These findings provided evidence that downregulation of miR-135a inhibits proliferation, migration, and invasion and promotes apoptosis of SFs in RA by upregulating the PIK3R2 coupled with inactivating the PI3K/AKT signaling pathway. The downregulation of miR-135a might be a potential target in the treatment of RA.

7.
Int Immunopharmacol ; 71: 132-138, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30897500

RESUMO

BACKGROUND: Diallyl Trisulfide (DATS) is an organosulfur compound extracted from garlic bulb, and exerts cardioprotective, anti-inflammatory, antioxidant, antimicrobial and anticancer effects. But its role in the pathogenesis of rheumatoid arthritis (RA) is unknown. Here we explored the influence of DATS on human fibroblast-like synoviocytes (FLS) isolated from RA patients and a mouse model of collagen-induced arthritis (CIA) and the underlying mechanism. METHODS: RA-FLS were cultured and treated with different concentrations of DATS. The CCK8 assay was used to assess cell proliferation while cell apoptosis was detected by flow cytometry and western blot. The IL-8, IL-6 and IL-1ß levels were determined using RT-qPCR and ELISA assay. The expression of proteins of the NF-κB and Wnt pathways were measured using western blot. Furthermore, the effect of DATS was also explored in vivo using the collagen-induced arthritis mouse model. The Th17/Treg pattern obtain from cells of spleen of collagen-induced arthritis mouse model was detected by flow cytometry. RESULTS: Our results showed that DATS could decrease cell viability and introduce apoptosis in RA-FLS. Furthermore, DATS significantly attenuated the production of key inflammatory cytokines induced by RA-FLS cells following treatment with tumor necrosis α (TNF-α) at a concentration of 100 µM or higher. This was due to its inhibitory effect on the NF-κB and Wnt pathway signaling in RA-FLS. Additionally, DATS decreased the production of inflammatory cytokines and regulated the immune function by restoring the balance between Th17 and Treg in CIA mouse model. CONCLUSIONS: In conclusion, DATS may serve as a potential curative agent for RA.


Assuntos
Compostos Alílicos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/fisiologia , Sulfetos/uso terapêutico , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Idoso , Animais , Apoptose , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Transdução de Sinais , Membrana Sinovial/patologia , Proteínas Wnt/metabolismo
8.
Clin Rheumatol ; 38(1): 107-115, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30123930

RESUMO

To estimate the mortality and describe the causes of death in a large multicenter cohort of hospitalized patients with SLE in China. This was a retrospective study of a nationwide SLE cohort (10 centers, 29,510 hospitalized patients) from 2005 to 2014 in China. Standardized mortality ratios (SMRs) were calculated for all death and were stratified by sex and age. Chi-square test was used to determine whether the major causes of death vary in age, sex, duration of SLE, disease activity, or medications. Comparison between dead patients and survival controls was used to identify the risk factors for mortality. Logistic regression analysis was used to evaluate the risk factors for mortality. A total of 360 patients died during the study period, accounting for 1.22%. The overall SMR was 2.13 (95% CI 1.96, 2.30), with a particularly high SMR seen in subgroups characterized by younger age. Infection (65.8%) was the most common cause of death, followed by lupus nephritis (48.6%), hematological abnormality (18.1%), neuropsychiatric lupus/NPSLE (15.8%), and interstitial pneumonia (13.1%). Cardiovascular disease and malignancy contributed little to the causes of death. Infection, in particular severe pulmonary infection, emerged as the foremost risk factor for mortality, followed by lupus encephalopathy. However, lupus nephritis and hematological abnormalities occurred more frequently in survival patients. SLE patients at a younger age of diagnosis have a poorer prognosis. Infection dominated the causes of death in recent China. Ethnicity and medications might account for the differences in causes of death compared with western populations.


Assuntos
Causas de Morte , Lúpus Eritematoso Sistêmico/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/complicações , Criança , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
9.
Clin Rheumatol ; 38(4): 1055-1062, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30498873

RESUMO

BACKGROUND: The association between several novel adiposity indices and hyperuricemia is inconclusive. Therefore, we aimed to investigate this association so as to provide theoretical support for the management of hyperuricemia in overweight/obese individuals. METHODS: A cross-sectional study was carried out among 174,698 adults. The values of body adiposity index (BAI), conicity index (CI), a body shape index (ABSI), body roundness index (BRI), visceral adiposity index (VAI), lipid accumulation product (LAP) index, and cardiometabolic index (CMI) were divided into four quartiles, and multivariate logistic analysis was used to analyze the association between them and hyperuricemia. Receiver operating characteristic curve and area under curve (AUC) were used to evaluate the power of predictions for hyperuricemia. RESULTS: After adjusting for confounding variables, LAP and CMI exhibited stronger association with hyperuricemia than other indices. The odd ratio (OR) for hyperuricemia in the highest quartile of the LAP and CMI was 2.049 (CI 95% = 1.824-2.302) and 4.332(CI 95% = 3.938-4.765). The AUC value of LAP was 0.632 (95% CI = 0.626-0.637), p < 0.001; and the AUC value of CMI was 0.687 (95% CI = 0.682-0.692), p < 0.001. The optimal cutoff values of LAP and CMI were 26.21 and 0.485, respectively. CONCLUSIONS: LAP and CMI, combination of WC and lipid parameters and reliable visceral adiposity indices, were strongly associated with hyperuricemia than other indices. So they could be potential monitoring indicators for hyperuricemia management in overweight/obese individuals.


Assuntos
Adiposidade/fisiologia , Índice de Massa Corporal , Hiperuricemia/fisiopatologia , Obesidade/fisiopatologia , Circunferência da Cintura/fisiologia , Adulto , Estudos Transversais , Feminino , Humanos , Hiperuricemia/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Fatores de Risco
10.
Chin Med J (Engl) ; 131(22): 2683-2692, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30425195

RESUMO

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population. Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population. Clinical Trial Identifier: NCT00856544 and NCT00413699.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Administração Oral , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
11.
Clin Rheumatol ; 37(1): 219-226, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28944421

RESUMO

The metabolic characteristics of rheumatoid arthritis (RA) or diabetes mellitus (DM) have been studied, but the metabolic abnormalities of RA patients complicated with DM are not completely understood. Therefore, we recruited RA patients with DM to investigate the metabolic abnormalities in these patients. We collected data of RA patients with DM and age- and sex-matched RA and DM patients from Changhai Hospital's electronic medical record system. Data of demographically matched healthy controls were also collected from the health management system of the Hangzhou Sanatorium of People's Liberation Army. Blood pressure, uric acid, glucose, and lipid levels were compared. The clinical data of RA with DM (n = 104), DM (n = 100), and RA (n = 100) patients and healthy controls (n = 100) were collected and compared. RA patients with DM had higher blood pressure and lower high-density lipoprotein cholesterol levels than the other three groups, a higher triglycerides (TG) level than healthy controls and RA patients, and a lower TG level than DM patients. RA patients with DM exhibited a relatively high proportion of metabolic abnormalities based on existing standards. Our study examined metabolic abnormalities in RA patients with DM for the first time, and our results suggest that clinicians should pay more attention to the metabolic abnormalities of RA patients with DM.


Assuntos
Artrite Reumatoide/sangue , Pressão Sanguínea/fisiologia , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Triglicerídeos/sangue , Idoso , Artrite Reumatoide/complicações , Diabetes Mellitus Tipo 2/complicações , Dislipidemias/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
12.
Oncotarget ; 8(8): 12649-12663, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28187436

RESUMO

Dishevelled (Dvl) not only links the canonical Wnt and non-canonical Wnt pathways but can also crosstalk with other pathways. As there is no systematic study to date on Dvl in rheumatoid arthritis (RA), we explored the impact of Dvl2 on proliferation and inflammatory cytokine secretion in RA fibroblast-like synoviocytes (FLSs). Expression of Dvl2 in RA synovial tissue and RA-FLSs was measured. Dvl2 was overexpressed in collagen-induced arthritis rats and human RA-FLSs,. the apoptosis and secretion of inflammatory cytokines were observed. Genetic changes and corresponding mechanisms caused by overexpressing Dvl2 in RA-FLSs were assessed. Dvl2 was found to be overexpressed in RA synovial tissue and RA-FLSs. Overexpression of Dvl2 increased apoptosis and inhibited inflammatory cytokine secretion by RA-FLSs in vivo and in vitro, and Dvl2 inhibited expression of anti-apoptotic and inflammatory genes. One possible mechanism is that Dvl2 decreases the nuclear translocation of P65 and inhibits its ability to bind to the promoters of NF-κB target genes. Our findings reveal an underappreciated role of Dvl2 in regulating inflammation and RA-FLS apoptosis and provide insight into crosstalk between the Wnt and nuclear factor-κB (NF-κB) pathways.


Assuntos
Apoptose/fisiologia , Artrite Reumatoide/metabolismo , Proteínas Desgrenhadas/metabolismo , NF-kappa B/metabolismo , Sinoviócitos/metabolismo , Animais , Artrite Reumatoide/patologia , Western Blotting , Separação Celular , Citocinas/biossíntese , Imunofluorescência , Humanos , Imunoprecipitação , Inflamação/metabolismo , Masculino , Reação em Cadeia da Polimerase , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Receptor Cross-Talk/fisiologia , Transdução de Sinais/fisiologia
13.
Clin Rheumatol ; 35(9): 2175-83, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27184046

RESUMO

The objective of the study was to evaluate the efficacy and safety of etanercept (Anbainuo) treatment in Chinese moderate to severe rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); 600 patients (360 in phase III-1 and 240 in phase III-2) poorly responding to MTX were enrolled in the study and randomized at a ratio of 2:1 into an Anbainuo treatment or control group. The study was designed as a 12-week double-blind, placebo-controlled period followed by a 12-week open-label study. The primary endpoint was the ACR20 response rate at week 12. Secondary endpoints included the ACR50, ACR70, ACR-N, and safety. At week 12, ACR20 response was observed in 60.9 % of the Anbainuo group-significantly higher than that of the control group (20.6 %). At week 24, the ACR20 response in the Anbainuo group increased to 70.2 %; there was no significant difference compared with that of the control group (61.8 %, P > 0.05). At week 12, the ACR50 and ACR70 responses of the Anbainuo group increased to 25.6 and 6.8 %, compared to 4 and 1 % in the control group (P < 0.001, P = 0.002). The ACR-N was 2.85 ± 6.73 vs. -3.24 ± 8.78 % in the control group (P < 0.001). During the first 12 weeks of treatment, 66 adverse events (AE) were reported in the Anbainuo group (15.6 %) and 21 AEs (10.5 %) occurred in the control group, whereby the rate of the Anbainuo group was slightly higher than the control group (P = 0.042). Severe adverse events (SAEs) occurred in the Anbainuo group (1.3 %) and one (SAE) occurred in the control group (0.5 %) (P = 0.19). Anbainuo displays a rapid onset of efficacy as well as good tolerance and safety in MTX-IR patients having moderate to severe RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Metotrexato/uso terapêutico , Receptores Tipo II do Fator de Necrose Tumoral/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Receptores Tipo II do Fator de Necrose Tumoral/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Retratamento , Índice de Gravidade de Doença , Falha de Tratamento , Resultado do Tratamento
14.
Exp Mol Pathol ; 100(1): 192-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26723864

RESUMO

OBJECTIVE: The purpose of our study was to elucidate the impact of microRNA-126 (miR-126) targeting PIK3R2 gene on cell proliferation and apoptosis of rheumatoid arthritis synovial fibro-blasts (RASFs) by regulating PI3K/AKT signal pathway. METHODS: The synovial tissue samples of this study were from 55 RA patients undergoing joint replacement and 27 healthy people undergoing joint repair due to trauma. The target genes of miR-126 were collected by the TargetScan and PIK3R2 as the direct target gene of miR-126 was confirmed by dual-luciferase reporter assay system. Our experiment had five groups including the blank control, miR-126 mimic, miR-126 mimic control, miR-126 inhibitor and miR-126 inhibitor control groups. Additionally, real-time quantitative polymerase chain reaction (RT-qPCR), Western-Blot, cell counting kit (CCK-8) and flow cytometry were carried out in this study. RESULTS: Compared with healthy individuals, the RA patients had increased miR-126, but decreased PIK3R2 mRNA expressions in the synovial tissues. Pearson correlation analysis indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (all P<0.05). When compared with the blank group respectively, the miR-126 mimic group had raising cell proportions in S and G2/M phases with reduced rate of cell apoptosis, while the miR-126 inhibitor group had raising cell proportions in G0/G1 and G2/M phases with increased rate of cell apoptosis (all P<0.05). Besides, compared with the blank control group, the miR-126 mimic group had declined expression of PIK3R2 protein with ascended expression of PI3K and p-AKT (all P<0.05), while the miR-126 inhibitor group had increased expression of PIK3R2 protein with decreased expression of PI3K and p-AKT (all P<0.05). CONCLUSION: Our study demonstrated that down-regulation of miR-126 may indirectly inhibit PI3K/AKT signaling pathway to disrupt the imbalance between growth and death of RASFs by targeting PIK3R2, which may be clinically helpful to find therapeutic strategies directed toward miR-126 function for RA patients.


Assuntos
Apoptose/fisiologia , Artrite Reumatoide/patologia , Proliferação de Células/genética , Fibroblastos/metabolismo , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Adulto , Idoso , Apoptose/genética , Artrite Reumatoide/genética , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Adulto Jovem
15.
Clin Rheumatol ; 35(1): 165-73, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24924603

RESUMO

This study is aimed at comparing the efficacy and safety of loxoprofen sodium hydrogel patch (LX-P) with loxoprofen sodium tablet (LX-T) in patients with knee osteoarthritis (OA). One hundred sixty-nine patients were enrolled in a randomized, controlled, double-blind, double-dummy, multicenter, non-inferiority trial of LX-P. Patients were randomly assigned to either LX-P or LX-T groups for a 4-week treatment. The primary efficacy endpoint was the proportion of patients with an overall improvement of ≥50%, and the secondary efficacy endpoint was the proportion of patients with an improvement of ≥25% from baseline in each of the seven main symptoms. The non-inferiority trial was based on a power of 80% and significance level of 2.5% with a non-inferiority margin of -10%. In both intention-to-treat (ITT) and per-protocol (PP) analyses, LX-P was as effective as LX-T in regard to the primary endpoint. In the ITT analysis, the difference between the two groups was 12.6% [95% confidence interval, -1.7 to 26.9%]. No significant differences were found between the two groups in any of the secondary efficacy outcomes. A lower incidence of adverse events was observed in LX-P group; however, the difference was not statistically significant. No serious adverse events were reported in the LX-P group, whereas one case was reported in LX-T group. Based on the present study, topical loxoprofen patch was non-inferior to oral loxoprofen in patients with knee osteoarthritis.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Fenilpropionatos/administração & dosagem , Comprimidos , Adesivo Transdérmico , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , China , Comorbidade , Método Duplo-Cego , Feminino , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Fenilpropionatos/efeitos adversos , Comprimidos/efeitos adversos , Adesivo Transdérmico/efeitos adversos , Resultado do Tratamento
16.
Artigo em Inglês | MEDLINE | ID: mdl-26471295

RESUMO

INTRODUCTION: Single-incision laparoscopic surgery (SILS) in gastric banding (SI-LAGB) has been reported to be a safe and technically feasible procedure among various operating methods. However, there is little evidence with regard to the question whether SI-LAGB has more advantages and should be recommended compared with conventional LAGB (CLAGB). Thus, this study was performed to assess the safety and efficacy of SI-LAGB. MATERIAL AND METHODS: A computerized search of the electronic databases PubMed and EMBASE was performed. Data regarding operative parameters, postoperative recovery parameters, follow-up time, percentage of excess weight loss, and postoperative complication were pooled and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. RESULTS: Ten comparative studies including 2,073 patients (1,038 patients who received SI-LAGB and 1,035 patients who received CLAGB) were included and analyzed. Compared with CLAGB, a similar weight loss could be obtained using SI-LAGB. The postoperative complications of SI-LAGB were within the acceptable range, but one study reported one perioperative death. SI-LAGB required a longer operative time. Other outcome variables, such as blood loss, days of hospitalization, pain score, and hospitalization costs, were not significantly different between the two groups. CONCLUSIONS: SI-LAGB might be a safe and effective alternative to C-LAGB when performed by experienced surgeons, but available data do not allow to give a definitive answer and randomized controlled trials are needed.


Assuntos
Cirurgia Bariátrica/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Cirurgia Bariátrica/efeitos adversos , Hospitalização/estatística & dados numéricos , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Duração da Cirurgia , Resultado do Tratamento , Perda de Peso
17.
Dis Markers ; 2015: 795043, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26435567

RESUMO

Interleukin- (IL-) 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA) and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP), were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1ß were analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28) and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA.


Assuntos
Artrite Reumatoide/sangue , Interleucina-1/sangue , Linfócitos T Auxiliares-Indutores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/patologia , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CCL2/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Humanos , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue
18.
Int Immunopharmacol ; 28(1): 802-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26292180

RESUMO

OBJECTIVE: Total glucosides of paeony (TGP) have been confirmed to exert anti-inflammatory and hepatoprotective effects. Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed. In this study, we investigated the effect of TGP on hepatic dysfunction caused by MTX and LEF in patients with active RA. METHODS: A total of 268 patients with active RA (disease activity score in 28 joints, DAS28>3.2) were enrolled in this study. All patients were randomly assigned to two groups, the therapeutic group in which patients were treated with TGP (1.8 g/day) combined with MTX and LEF (MTX 10mg/week plus LEF 20mg/day) while in the control group, patients were treated without TGP up to 12 weeks. The efficacy and liver abnormalities were observed. RESULTS: The incidence of abnormal liver function within 12 weeks in TGP group was significantly lower than that in control group (11.38% vs 23.26%, P=0.013). The proportion of patients with ALT/AST >3 times ULN (upper limits of normal) was significantly lower in TGP group than control group (1.63% vs 7.75%, P=0.022). More patients achieved remission, good and moderate response in TGP group than control group at 4, 8 and 12 weeks, but the difference was not significant (P>0.05). The proportions of all adverse events were comparable in the two groups except for diarrhea. CONCLUSIONS: Our study demonstrates that TGP can significantly reduce the incidence and severity of liver damage caused by MTX+LEF in the treatment of active RA patients.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glucosídeos/uso terapêutico , Isoxazóis/toxicidade , Metotrexato/toxicidade , Paeonia/química , Adolescente , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Quimioterapia Combinada , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/isolamento & purificação , Humanos , Isoxazóis/administração & dosagem , Isoxazóis/uso terapêutico , Leflunomida , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
19.
Rheumatol Int ; 34(11): 1519-27, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24671501

RESUMO

To assess the clinical efficacy as well as safety profiles of Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein, versus placebo in the treatment of Chinese active rheumatoid arthritis (RA) patients with an inadequate clinical response to methotrexate (MTX). In this 24-week, randomized, double-blind, placebo-controlled multicenter study, a total of 440 Chinese patients with active RA with an inadequate response to MTX were randomly assigned to receive Leining (10 mg/kg) or placebo. Clinical response was assessed using the American College of Rheumatology 20 % improvement criteria ACR20, ACR50, and ACR70, with ACR20 as the primary major endpoints. Disease activity scores in 28 joints with erythrocyte sedimentation rate assessment (DAS28-ESR) were used to evaluate disease activity. After 24 weeks of treatment, significantly more patients in Leining group achieved ACR20 response than those in placebo group (70.61 vs. 46.36 %; p < 0.001). Similarly, ACR50 and ACR70 responses of Leining group were significantly higher than those of placebo group (40.30 vs. 22.73 %; p < 0.001 and 16.67 vs. 7.27 %; p < 0.05, respectively). DAS28-ESR in Leining group was significantly reduced compared to that in placebo group, with greater clinically meaningful (>1.2 unit) improvement (54.85 vs. 29.09 %, p < 0.05). Both the rates of remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR < 3.2) were greater in the Leining group than those in the placebo group (12.42 vs. 2.73 %; p < 0.05 and 15.45 vs. 2.73 %; p < 0.05 respectively). The overall incidence of adverse events was similar in both Leining and placebo groups. No neutralizing antibodies were detected. Leining demonstrated clinically meaningful efficacy compared with placebo in Chinese patients with active RA despite MTX therapy. Administration of Leining in combination with MTX for 24 weeks was well tolerated.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunoconjugados/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/etnologia , Artrite Reumatoide/imunologia , Grupo com Ancestrais do Continente Asiático , Sedimentação Sanguínea , China/epidemiologia , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Humanos , Imunoconjugados/efeitos adversos , Imunossupressores/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/efeitos adversos , Indução de Remissão , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
20.
Mod Rheumatol ; 24(5): 793-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24372293

RESUMO

OBJECTIVES: To estimate the diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjögren's syndrome (pSS). METHODS: Sixty-four pSS subjects and 108 non-pSS patients were prospectively enrolled in this study. Serum anti-alpha-fodrin IgA and IgG were detected by ELISA in a blind fashion. The diagnostic accuracy of anti-alpha-fodrin antibodies was assessed by receiver operating characteristic (ROC) curve analysis. Logistic regression was used to investigate whether anti-alpha-fodrin antibodies could improve the accuracy of pSS diagnosis if used in addition to anti-SSA and anti-SSB. RESULTS: The areas under the ROC curves for anti-alpha-fodrin IgG and IgA were 0.69 (95% confidence interval (CI): 0.60-0.77) and 0.63 (95% CI: 0.54-0.72), respectively (P < 0.01 for both). The optimal diagnostic thresholds for anti-fodrin IgG and IgA were 11.75 U/ml and 9.75 U/ml, respectively, with a sensitivity of 0.59 and 0.55, and a specificity of 0.75 and 0.73, respectively. Anti-alpha-fodrin IgG and IgA antibodies were associated with pSS after adjustment for anti-SSA and anti-SSB. CONCLUSIONS: Anti-alpha-fodrin IgG and IgA antibodies are useful diagnostic markers which may improve the accuracy of pSS diagnosis.


Assuntos
Autoanticorpos/sangue , Proteínas de Transporte/imunologia , Proteínas dos Microfilamentos/imunologia , Síndrome de Sjogren/diagnóstico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Síndrome de Sjogren/sangue , Síndrome de Sjogren/imunologia
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