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Objective:To evaluate the association between the efficacy and safety of metformin and the influence of variants in SLC47A1 rs2289669 G>A polymorphism in the treatment of systemic lupus erythematosus (SLE).Methods:A multicenter, randomized, double-blind, placebo-controlled trial was conducted. Patients were consented at enrollment for blood donation for genotyping, and their peripheral blood were used to detect the distribution frequency of SLC47A1 mutations. The major or mild/moderate flares defined by modified safety lupus erythematosus national assessment (SELENA)-systemic lupus erythematosus disease activity index (SLEDAI) Flare Index (SFI) and adverse events were recorded at 12 months of follow-up. The correlation between efficacy/safety and genotype was analyzed. Student's t test and χ2 test was used to assess the continuous variables and categorical variables. Results:Between May 24, 2016, and Dec 13, 2017, a total of 31 patients in the metformin group and 35 in the placebo group were detected. There were no statistical significant differences in the clinical manifestations, SELENA-SLEDAI scores, and therapy of the participants at baseline. There was no significant difference in the frequency of AA genotype, GA genotype, and GG genotype of SLC47A1 rs2289669 distribution between the metformin group and the placebo group. In the metformin group, patients who flared had a lower frequency of A alleles than those non-flared [25%(4/16) vs 61%(28/46), χ2=6.116, P=0.019 8]; the flare rate was significantly lower in patients with AA genotype than in GG genotype [0%(0/8) vs 57%(4/7), χ2=6.234, P=0.012 5]. The infection rate was lower in the metformin group than that in the placebo group [38%(12/31) vs 69%(24/35), χ2=5.913, P=0.015 0], but there was no significant difference among different genotypes in the metformin group. Compared to GG geno-type, AA genotype showed a trend of decrease in infection rate[38%(3/8) vs 72%(5/7), χ2=1.727, P=0.188 8]. Conclusion:Metformin has a favorable safety profile and may reduce the frequency of flares in SLE patients with low-grade lupus disease activity. The metformin therapeutic efficacy in SLE is relevant to the SLC47A1 gene polymorphism. Patients of the AA genotype may benefit most from metformin than those of the GG and GA genotypes.
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Objective To analyze the roles of B-cell ccaffold protein with ankyrin repeats 1 (BANK1) in collagen-induced arthritis (CIA) murine model and the correlation with disease severity.Methods CIA murine model were established and evaluated.In different disease stages,the serum levels of anti-C Ⅱ auto-antibodies and BANK1 were detected by electrochemiluminescence immunoassay(ELISA).Moreover,the expression of BANK1 mRNA in peripheral blood cells were detected by real-time polymerase chain reaction (PCR) and its correlation with clinical scores was analyzed.Then the percentage of BANK1 expression in B cells in spleen and draining lymph nodes were detected by flow cytometry and the level of BANK1 protein in spleen was detected by Western blotting according to the results afore mentioned.The data was analyzed by Statistical Product and Service Solutions (SPSS) Stastistics 21.0 and figures were made with Graph Pad Prism 6.Repeated measure ANOVA was used to assess differences between the two groups.Correlations were analyzed by Spearman correlation analysis.Linear regression analysis was done when a correlation was identified.Results The incidence of CIA was over 90％.The clinical scores of arthritic mice was positively correlated with the serum levels of anti C Ⅱ total IgG antibody (r=0.717 5,P ＜0.01),anti C] IgG2a antibody (r=0.675 3,P＜0.01) and anti C Ⅱ IgG2b antibody (r=0.889 4,P＜0.01) respectively.The BANK1 level in the serum and the BANK1 mRNA expression were significantly decreased in different disease stages in CIA mice when compared with normal mice.The negative correlation between the BANK1 mRNA expression and clinical scores (r=-0.485 4,P＜0.01) was observed.The percentage of BANK1 +CD19+ cells in spleen and draining lymph nodes and the level of BANK1 protein in spleen were reduced in CIA as well.Conclusion Along with the disease progress in CIA,BNK1 expression is declined,which weakens the negative regulation of BANK1 on B cells.This change goes hand in hand with the severity of arthritis.
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Objective To investigate the relationship between interleukin (IL)-34 and bone erosions in psoriatic arthritis (PsA) patients.Methods Forty PsA patients,20 psoriasis (Ps) patients and 20 healthy volunteers were recruited into this study.The levels of IL-34 and osteoclast related cytokines [including tumor necrosis factor (TNF)-α,receptor activator of nuclear factor-κB ligand (RANKL),osteoclast precursors (OPG)] were detected in the serum samples of all subjects.The correlations among IL-34,the number of osteoclast precursors (OCP),disease activity and imaging scores were analyzed.All data were analyzed by graphpad prism 6.Differences between groups was analyzed with One-way analysis of variance,q tests,and Spearman's correlation was used to explore the relation between disease activity/radiographic scores and laboratory results and followed by linear regressions.Results The serum level of IL-34 in patients with PsA [(328±476) pg/ml] was higher than that in Ps [(33±52) pg/ml,q =3.92,P＜0.01] and healthy controls [(32±32) pg/ml,q =3.93,P＜0.01],the erosive PsA group were higher than the non-erosive PsA group [(449±527) pg/ml and (47±24) pg/ml,q=4.04,P＜0.01].The levels of TNF-α,RANKL and OCP in patients with PsA [(125±79) pg/ml,(488± 475) pg/ml and (17.7±4.8) 5 sigh views] were higher than those in PS [(40±22) pg/ml,(26±3) pg/ml and (5.2± 0.8),q=7.32,6.14 and 2.94,P＜0.01] and healthy controls [(41±19) pg/ml,(65±8) pg/ml and (6.2±1.8),q=6.67,5.62 and 2.71,P＜0.01],whereas the OPG/RANKL ratio in PsA patients (0.5±0.4) was significantly lower than Ps patients (4.3±2.7,q=-3.30,P＜0.01) and healthy controls (1.8±0.6,q=-1.72,P＜0.01).IL-34,TNF-α and RANKL levels were all positively correlated with OCP (r=0.10,P＜0.05;r=0.12,P＜0.05;r=0.13,P＜0.(5,respectively).Conclusion The level of IL-34 is not only high in patients with PsA but also positively correlates with the number of OCP.In PsA,IL-34 is probably related to the OCP and osteoclast differentiation,and further participates in the process of bone destruction.Therefore,IL-34 is promising to become a new target or alternative choice for the treatment of PsA.
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Objective To observe the bone metabolism of psoriatic arthritis (PsA) and investigate the roles of some bone metabolism markers such as tartrate-resistant acid phosphatase 5b (TRACP5),C-terminal telopeptide of collagen-Ⅰ (CTX-Ⅰ) and BALP in PsA patients with bone destructions.Methods Sixty-five cases of psoriatic arthritis,30 cases of psoriasis and 30 cases of healthy people were enrolled.Bone mineral densities of lumbar spines and the left femoral necks were measured for all PsA patients using dual energy X-ray absorptiometry.The Serum levels of TRACP5b,CTX-Ⅰ,BALP of healthy controls,Ps and PsA patients were measured.The PsA group was further divided into bone destruction group and none bone destruction group by image datasets.The levels of TRACP5b,CTX-Ⅰ,BALP,PsAJAI,ESR and CRP from each group were detected.Mann-Whitney and x2 test were used for statistic analysis.Results TRACP5b levels of the healthy controls,Ps and PsA patients were (0.9±0.4),(0.7±0.5) and (2.0±1.4) U/L respectively,and were significantly higher in the PsA patients than those of the other two groups (Z=-3.698,-3.638; P＜0.05).The CTX-Ⅰ levels of these three groups were (0.9±0.8),(0.6±0.7) and (2.6±1.8) ng/ml respectively,and were also dramatically higher in the PsA patients than the other two groups (Z=-5.262,-5.734; P＜0.05).BALP levels of each group were (22±4),(22±4) and (25±7) U/L,and were also evidently higher in the PsA patients than patients in the other two groups (Z=-2.214,-2.000; P＜0.05).Meanwhile,the levels of TRACP5b [(2.6±1.4) U/L],CTX-Ⅰ [(3.1±1.8) ng/ml] and BALP [(26±7) U/L] were significantly higher in bone destruction group than those in the none bone destruction group [(1.2±1.0) U/L,(1.9±1.6) ng/ml,(23±6) U/L,Z=-3.544,-3.429,-2.083; P＜0.05].Conclusion The high levels of TRACP5b,CTX-Ⅰ and BALP in PsA indicate that there is bone metabolism imbalances in PsA.And the high levels of TRACP5b,CTX-Ⅰ and BALP in the bone destruction group suggest that the rises of TRACP5,CTX-Ⅰ and BALP levels may be related with bone erosions.
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ObjectiveTo explore the effect of osteoclasts and osteoprotegerin/receptor activator of nuclear factor-kappa B ligand (OPG/RANKL) system on bone destruction of psoriatic arthritis.MethodsThe peripheral blood mononuclear cells from 41 psoriatic arthritis (PsA) patients,20 osteoarthritis (OA) patients and 24 healthy controls were cultured to become osteoclasts.After 14 days,cytochemistry method was used to detect tartrate-resistant acid phosphatase (TRAP) expression.At the same time,enzyme-linked immuno sorbent assay(ELISA) was used to measure the levels of serum OPG and RNAKL for all cases.At the same time,the clinical and laboratory examinations of the PsA were collected.Statistical analysis was conducted with one-way ANOVA and Spearman's correlation.ResultsSignificantly higher OC production was observed in the peripheral blood of PsA patients[(17.7±4.8)/view field] than that of the healthy controls[(6.4±1.6)/view field] and OA patients [(6.5±l.6)/view field].The levels of RANKL were significantly higher in PsA patients [(178±38) pg/ml] than those in the other two groups [(32±4) pg/ml and (67±17) pg/ml].There was significant difference between the PsA group with bone destruction and without destruction in the levels of OC and RANKL [(17.6±0.9) /view vs(7.9±1.3) /view and(199±72) pg/ml vs(128±44) pg/ml,P＜0.01].Imaging scores was positively correlated with the levels of OC and RANKL in PsA patients (P＜0.05).ConclusionIn PsA,there are significantly more OC and higher RANKL in the peripheral blood than those of the controls.The high levels of OC and RANKL are closely related with bone destruction.OC and RANKL are useful in identifying bone destruction.
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Objective The aim of the study was to observe the features of nail fold microcirculation in systemic sclerosis (SSc) patients and to compare these findings in SSc patients with patients with other connective tissue diseases.Methods Forty patients with SSc and thirty-seven patients with other connective tissue diseases were included in the study and all the patients reported symptoms of Raynaud's phenomenon in the hands were also included.Nail fold capillaroscopy (NFC) was performed and the abnormality of nail fold microcirculation between the two groups were compared.The relations between nail fold capillaroscopic findings and clinicolaboratory parameters in SSc patients were analyzed.Statistical analysis were carried out by t-test and Chi-square.Results The loss of capillaries and dilated and giant capillaries and hemorrhage as well as neoangiogenesis were hallmarks of the scleroderma capillary findings,which could be detected by nail fold capillaroscopy.The abnormalities of nail fold microcirculation in SSc patients were more severe and more specific than those in other connective tissue disease patients.The total scores of nail fold capillaroscopy test were obviously higher in SSc patients with lung or esophagus involvement than those patients without these organ involvement,meanwhile,the total scores of nail fold capillaroscopic findiugs were elevated in SSc patients with anti-Scl70 antibody than those with negative group.Conclusion The nail fold capillaries of patients with SSc have specific abnormalities,and nail fold capill-aroscopy could distinguish between SSc and other connective tissue diseases,therefore it could be used as a promising tool for early detection of patients who may have the potential to develop scleroderma and it is also helpful in assessing disease severity.
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Literatures on arrhythmia induced by acute organophosphorous pesticide poisoning published in domestic journals from 1979 to 2010 were searched. Total 3468 cases of acute organophosphorous poisoning were collected and analyzed. The average abnormal ECC rate was (53 ±15)%(35. 4% -68. 4% ) in acute organophosphorous poisoning, the most common ECG abnormalities were ST-T segment changes (26. 5% ) and sinus tachycardia (16. 6% ). The rate and severity of ECG abnormalities were increased with the severity of organophosphorous poisoning(x2 = 33. 253,P < 0. 01). The most common causes of death in acute organophosphorous poisoning were ventricular tachycardia and ventricular fibrillation (26.2%).
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<p><b>OBJECTIVE</b>To determine whether and to what degree the activity of cholinesterase(ChE) is inhibited by dimehypo at different doses of dimehypo [scientific name: 2-dimethylamine-1,3-bi(sodium hyposulfit)].</p><p><b>METHOD</b>Rats were dosed with dimehypo or methamidophos orally, and were randomly divided into four subgroups according to the pesticide doses, which were 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimethypo and methamidophos is 342 mg/kg and 20 mg/kg respectively). The activity of ChE in blood was determined before and 30 min, 1, 2, 4 and 24 h after exposure. The modified Ellman Method was employed to measure the activity of ChE.</p><p><b>RESULT</b>1/16 LD50 dose of dimehypo did not affect the activity of ChE. When the dose increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of dimehypo inhibited the activity of ChE by 35.9% compared with that of control group(P < 0.01). In rats dosed with methamidophos, even 1/16 LD50 dose inhibited the activity of ChE by 42.4% compared with that of control group. When the dose of methamidophos increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of methamidophos inhibited the activity of ChE by 52.9%. The activity of ChE in the rats dosed with dimehypo at various doses was significantly lower than that in the rats dosed with corresponding doses of methamidophos(P < 0.01).</p><p><b>CONCLUSION</b>Higher doses of dimehypo may inhibit the activity of ChE. However, as compared with methamidophos, dimehypo is a weaker inhibitor of ChE.</p>
Subject(s)
Animals , Rats , Cholinesterase Inhibitors , Toxicity , Cholinesterases , Blood , Dose-Response Relationship, Drug , Insecticides , Toxicity , Lethal Dose 50 , Organothiophosphorus Compounds , ToxicityABSTRACT
<p><b>OBJECTIVE</b>To investigate the activity of ChE in rats poisoned by dimehypo and then treated with pralidoxime methylchloride or unithiol.</p><p><b>METHOD</b>Rats were divided into control group (dimehypo); intervention groups [dimehypo plus pralidoxime methylchloride or dimehypo plus unithiol (sodium dimercaptopropanesulphonate)]. Rats were dosed with 4 different doses of dimehypo: 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimehypo is 342 mg/kg). After being poisoned with dimehypo orally, rats were immediately injected intramuscularly with pralidoxime methylchloride or unithiol. The activity of ChE in blood was detected before and 1/2, 1, 2, 4 and 24 h after poisoning in dimehypo and intervention groups.</p><p><b>RESULT</b>The ChE activity of four dose subgroups at 1 h after poisoning were (1.04 +/- 0.21), (0.84 +/- 0.12), (0.71 +/- 0.12), (0.66 +/- 0.07) U/ml respectively; the ChE activity of pralidoxime methylchloride intervention groups were (1.01 +/- 0.18), (1.17 +/- 0.11), (1.01 +/- 0.04), (1.03 +/- 0.12) U/ml respectively; and the ChE activity of unithiol intervention groups were (1.15 +/- 0.15), (1.26 +/- 0.27), (1.08 +/- 0.08), (1.04 +/- 0.12) U/ml respectively. The inhibited ChE in blood was recovered by either treatment with pyraldoxime methylchloride or unithiol. These two drugs had similar effects of recovering the activity of ChE(P > 0.05), but at higher doses(1/4 and 1/2 of LD50) the effects of both were not so good.</p><p><b>CONCLUSION</b>Pralidoxime methylchloride and unithiol could partly recover the activity of ChE inhibited by dimehypo.</p>