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Objective To evaluate the safety and drug adherence of tocilizumab(TCZ)in patients with moderate to severe rheumatoid arthritis(RA)in routine clinical practice. Methods This 24 week single center observational study recruited patients with moderate to severe RA. Therapy adherence rate was calculated by actual dosing/expected dosing×100%. Efficacy end points included physician global assessment of disease activity(PGA),patient global assessment of disease activity(PtGA),28-joint disease activity score(DAS28)and so on. Safety was evaluated by recorded adverse events (AEs). Results Sixty patients were enrolled with a mean (SD) treatment adherence of (67±27)%. PGA, PtGA, pain assessment (VAS), TJC and SJC all decreased during this study. At the 12th week, 25%(6/24) and 29%(7/24) of the patients achieved DAS28 remission and EULAR good response,respectively.Eighteen AEs were recorded,of which only 2 were severe AEs(SAEs)and neither was related to TCZ. Conclusion TCZ is a highly safe treatment for decreasing disease activity in patients with moderate to severe RA in China.However,drug adherence still need to be improved.
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Primary Sj?gren′s syndrome ( pSS) is a kind of chronic autoimmune disease affecting many organs of the body. The pathogenesis of pSS is still debated. Epstein-Barr virus(EBV), also called human herpesvirus-4, belongs to the herpesviridae family. Researchers have found that EBV is associated with pSS. With the deepening of researches, more evidences and opinions about the participation of EBV in the pathogenesis of pSS have emerged. EBV can cause the development of pSS in multiple ways. In this re-view, we summarize the roles of EBV in the pathogenesis of pSS.
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Objective:To study the pathological mechanism of the inducible co-stimulator molecular and ligand ( ICOS/ICOSL) in Graves disease animal.Methods:45 out-bred BALB/c mice were randomly divided into three groups with 15 rats in each group;using gene gun to deliver different plasmid injection.Group A was delivered with pCDNA3.0-mICOSL and pCDNA3.0-hTSHR, Group B with pCDNA3.0-hTSHR and null pCDNA3.0 with Group C for immunization as the control group.The concentration of serum free thyroxine immunization was deter mined with immunoassay and serum thyrotropin receptor antibody ( TRAb ) with ELISA, supernatant of IFN-γconcentration in mouse spleen cells was measured with radioimmunoassay,and hTSHR transected CHO cells were incubated to detect the concentration of cAMP to deter mine autoantibody TRAb activity.Results: After plasmid injection serum FT4 level in Group A (0.49±0.25) pg/ml ( q=6.571,P=0.023) was higher than that in Group C,the standard rate was higher than Group B and C (χ2=14.47,P=0.005).IFN-γconcentration of mice spleen cultured supernatant in Group A (1.88±0.41) pmol/L was significantly higher than the other two groups.The activity of autoantibody TRAb in Group A 188.3 (179.7-260.2) %was higher than that in the other two groups ( P=0.027 ) .Conclusion: Exogenous delivery of pCDNA3.0-mICOSL plasmid in GD mice could stimulate the spleen lymphocytes to secrete more IFN-γ,increase the activity of TRAb autoantibodies and might lead to upregulation of immune response in Graves animal model in vivo.
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Objective To investigate the clinical features and mechanism and feasibility of plasma exchange (PE) in treating systemic lupus erythematosus (SLE) complicated with acute pancreatitis (AP). Methods A retrospective analysis of SLE associated with AP was done based on the HIS in Tongji Hospital. Totally 24 SLEAP patients were admitted to Tongji hospital from March 2006 to May 2014. Patientsˊ serum amylase, lipase and interleukin (IL)-6 concentration were measured before and after plasma exchange. According to different therapy strategy, patients were divided into two groups. Fifteen patients treated with plasma exchange combination with glucocorticosteroid (GC) were classified as Group A, the other 9 patients who were treated with GC only were classified as group B. At baseline and after treatment, the serum lipid concentration, average daily glucocorticosteroid dosage between group A and B were compared with ANOVA and serum IL-6 concentration between roup A and B were compared with Wilcoxon rank test. Results SLEDAI score in group A patients at baseline (16 ±5) was no statistically different from that in group B (18 ±4) (t=1.31, P=0.320). Average daily GC dosage in group A 31.0 (20.50, 30.08)mg/d was significantly less than that in group B 47.85 (45.58, 59.23) mg/d (Z=35.50, P= 0.002). Serum IL-6 levels in group A and B at baseline was not significantly different 13.14 (11.12,16.57) mg/L vs 14.63 (11.37, 16.37) mg/L (Z=12.20, P=0.300), after 2 weeks treatment, IL-6 level, which was 9.16 (7.93, 10.75) mg/L, decreased significantly in group A while it didnˊt show tendency of decrease in group B, which was 13.62(9.29, 17.63) mg/L (Z=28.50, P=0.039). Serum lipid concentration after 2 weeks therapy in Group A [TC=(5.02 ±0.53) mmol/L, TG=(1.46 ±0.44) mmol/L] decreased significantly compared to baseline [TC=(6.11±0.50) mmol/L, TG=(2.14±0.65) mmol/L] (F=4.46, P=0.010; F=6.09, P=0.002), while similar tendency wasnˊt observed in group B (F=1.57, P>0.05). Conclusion PE combined with GC could lower serum IL-6 levels, reduce the amount of GC and lower serum lipid to improve prognosis. Therefore it might be a safe and effective way and is worthy of continuing to explore its feasibility.
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Clinical practice teaching in out-patient department is an important part of general internal clinical teaching for medical students. From 2010, eight-year program medical students in Huazhong University of Science and Technology began their clinical rotation practice in the out-patient department of general internal medicine. The one-on-one tutoring style was used in clinical teaching. We combined teacher demonstration teaching method with teacher supervision teaching method in clinical practice, and carried out periodical case discussion. At the end of each rotation stage, regular teaching evaluation and examination was taken. It has been proved that our teaching mode can not only help the students improve their professional and practical levels of clinical skills, and also help them gain the clinical working abilities and the professional spirits, which is worthy of further promotion.
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Objective To establish whether Wnt-signaling pathway plays a role in mice β-cell function and/or survival in vitro. Methods Mice NIT-1 beta cells were cultured in media with glucose concentration of 33.3 mmol/L and the cytokines interleukin-1β, interferon-γand tumor necrosis factor-α with or without the addition of purified Wnt3a protein in vitro. Subsequently, β-cell apoptosis by Tunnel and flow cytometry, and β-cell proliferation by BrdU were analyzed. Total RNA was extracted to measure gene expressions by real-time PCR.Results Incubations of NIT-1 cells with high glucose and cytokines resulted in an increase in β-cell apoptosis and decrease in β-cell proliferation (P<0.01). In contrast, treatment with Wnt3a protein protected β-cell from glucose and cytokines-induced apoptosis through up-regulating the expressions of above Pitx2、 TCF7L2. Conclusions Wnt-signaling regulates the proliferation of pancreatic β-cell, and protectes β-cell from glucotoxicity and cytokine toxicity with respect to proliferation and apoptosis.
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Objective To investigate the effect of small interference RNA (siRNA) targeting at 11β-hydroxysteroid dehydrogenase type 1 on the glucose-stimulated insulin secretion (GSIS) in pancreatic β cell line NIT-1 cell.Methods siRNA plasmid vectors specifically targeting at 11β-HSD1 gene were constructed,named as olig886,oligo866 and scrabble control for oligo886,then tansfected into NIT-1 cells.The expression of 11β-HSD1 was detected by RT-PCR and Western blot.O1igo886 vector was transfected into the NIT-1 cells in 25 mmol/L glucose concentrations medium.The insulin secretion level was measured in GSIS test.Results After treatment with 11β-HSD1 siRNA,the mRNA level of 11β-HSD1 in NIT-1 cell was decreased by 78.1%±2.9% and 51.7% ±2.7% inolig886 and oligo866 group respectively.The protein of 11β-HSD1 were decreased by 82.2% ±2.1% and 56.5%±2.0 % respectively.After transfected by olig 8 8 6 vector,the insulin secretion increased in NIT -1 cell.Conclusion 11β-HSD1 gene silencing may improve GSIS in NIT-1 cell 11β-HSD1 regulate local glucocorticoid metabolism in pan-creatic islet and affect the function of insulin secretion.
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A total of 96 patients with Graves'disease(GD)were followed for one and half years to observe the effect of antithyroid drugs(ATD)treatment.Serum TRAb,total iodine concentration and CD80 mRNA expression of peripheral blood monouclear ceils were measured.Logistics regression analysis was conducted with the combination of above parameters.Those GD patients with high level of TRAb,positive family history of GD, increased expression of CD80 and early age of onset were more inclined to relapse after ATD treatment.
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The aim of this investigation was to determine whether a PPARgamma2 Pro12Ala polymorphism was associated with insulin resistance, beta-cell function and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes (HbAC1 < 6.0) were investigated, including 132 hypertensive diabetic (HTD) subjects, 157 normotensive diabetic (NTD) subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test (OGTT). Biochemical measurements (high-density lipoprotein (HDL) and low-density lipoprotein-cholesterol (LDL), triglycerides) and PPARgamma2 Pro12Ala genotype were also determined. And insulin resistance and beta-cells function was assessed by HOMA-IR and HOMA-beta respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group (3.03%) than in the non-hypertension group (5.7%) (P < 0.05) after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level (P = 0.0127), and better glucose tolerance 60 min after oral glucose (P = 0.0361). Moreover, plasma insulin concentrations at 60 min was lower than those without A variant (P = 0.0275), and both hypertensive Ala/Pro in HOMA-beta (P = 0.0455) and AUC for insulin (P = 0.0473) were higher, and HOMA-IR was lower (P = 0.0375) as compared with hypertensive Pro/Pro subjects. No association was observed between Pro12Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARgamma2 gene may improve insulin resistance and ameliorate beta-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPAR gamma2 on glucose homeostasis and insulin resistance.
Subject(s)
Alanine/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Hypertension/complications , Hypertension/genetics , Insulin Resistance/genetics , Insulin-Secreting Cells/physiology , Mutation , PPAR gamma/genetics , Proline/geneticsABSTRACT
The aim of this investigation was to determine whether a PPARγ2 Pro12Ala polymorphism was associated with insulin resistance, β-cell function and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes (HbAC1＜6.0) were investigated, including 132 hypertensive diabetic (HTD) subjects, 157 normotensive diabetic (NTD) subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test (OGTT). Biochemical measurements (high-density lipoprotein (HDL) and low-density lipoprotein-cholesterol (LDL), triglycerides) and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group (3.03 %) than in the non-hypertension group (5.7 %) (P＜0.05) after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level (P=0. 0127), and better glucose tolerance 60 min after oral glucose (P=0. 0361). Moreover, plasma insulin concentrations at 60 min was lower than those without A variant (P = 0. 0275), and both hypertensive Ala/Pro in HOMA-β (P = 0. 0455) and AUC for insulin (P=0. 0473) were higher, and HOMA-IR was lower (P=0. 0375) as compared with hypertensive Pro/Pro subjects. No association was observed between Pro12Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPAR γ2 on glucose homeostasis and insulin resistance.