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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.
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Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the sacroiliac joints, spine and peripheral joints. In China, standardized diagnosis and treatment of AS is still to be popularized. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed standardization of diagnosis and treatment of AS. The purposes are: (1) to standardize the diagnosis and evaluation of AS; (2) to promote rational use of non-steroidal anti-inflammatory drugs, biological as well as traditional disease modifying anti-rheumatic drugs, so as to improve the patient′s quality of life.
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Objective:To explore the diagnostic value of hand tenosynovitis in rheumatoid arthritis (RA).Methods:Seventy-six RA patients were enrolled for hands ultrasound examination. Forty-five RA patients with synovitis and tenosynovitis were selected as the study group, clinical characteristics, laboratory test results, disease activity score for 28 joint counts (DAS28), were evaluated and assessed, and the health assessment questionnaire (HAQ) was filled out, and semi-quantitative classification the ultrasonic indicators (synovial hyperplasia, synovitis, tenosynovitis, bone erosion) were also assessed. Forty-two non-RA patients with hand tenosynovitis were selected as the control group. Mann-whitney U test, Spearman correlation and paired U test were used for statistical analysis. Results:① In the RA group, synovial hyperplasia [7.50(3.00, 17.50)], synovitis [6.00(2.00, 14.00)], tenosynovitis [6.00(2.00, 12.00)], bone erosion [0.50(0.00, 4.00)] were statisticantly different when compared with in non-RA group in hyperplasia [5.00(3.00, 6.00)], synovitis [3.00(2.00, 4.30)], tenosynovitis [2.00(1.00, 3.00)], bone erosion [0.00(0.00, 1.00)] ( Z=2.143, P=0.032; Z=2.756, P=0.006; Z=5.560, P<0.01; Z=2.550, P=0.011). ② In the RA group, synovial hyperplasia and synovitis were positively correlated with swollen joint counts (SJC), tender joint counts (TJC), platelet (PLT), C-reactive pro-tein (CRP) and DAS28 [synovial hyperplasia ( r=0.806, P<0.01; r=0.486, P<0.01; r=0.326, P<0.05; r=0.450, P<0.01; r=0.413, P<0.01); and synovitis ( r=0.819, P<0.01; r=0.446, P<0.01; r=0.351, P<0.05; r=0.481, P<0.01; r=0.412, P<0.01)]. Tenosynovitis was positively correlated with SJC, CRP and DAS28 ( r=0.436, P<0.01; r=0.496, P<0.05; r=0.359, P<0.05) , bone erosion was positively correlated with disease course and anti-cyclic citrullinated peptide (CCP) antibody ( r=0.418, P<0.01; r=0.338, P<0.05) . ③ The sensitivity of synovial hyperplasia, synovitis, tenosynovitis, bone erosion and synovitis combined with tenosynovitis for the diagnosis of RA was 0.41, 0.61, 0.57, 0.48, 0.61 and the specificity was 0.95, 0.76, 1, 0.83, 0.93, respectively. ④ The largest area under the ROC curve was tenosynovitis [area under the curve (AUC)=0.841], the area under the curve of tenosynovitis and synovitis combined with tenosynovitis was significantly different from synovitis hyperplasia, synovitis and bone erosion [tenosynovitis( Z=3.291, P=0.001; Z=2.651, P=0.008; Z=3.032, P=0.002); synovitis combined with tenosynovitis( Z=4.346, P=0.001; Z=3.753, P=0.001; Z=2.547, P=0.012)]. Conclusion:Synovitis has a high sensitivity for the diagnosis of RA, and tenosynovitis has a high specificity for the diagnosis of RA, synovitis combined with tenosynovitis can improve the specificity for the diagnosis of RA.
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Objective The purpose of this study was to evaluate the degree of skin thickening of patients with systemic sclerosis (SSc) by high-frequecy ultrasound,as well as the value of ultrasound.Methods Thirty-one patients with SSc and 31 age-matched and sex-matched healthy control subjects were enrolled.Skin thickness,modified Rodnan skin score (mRss),disease activity index (DA1) and other clinical parameters within and between groups were compared using SPSS 21 software.Student's t test,x2 test or nonparametric testing was performed to compare between groups.The Pearson or Spearman methods were used to test correlation.Sensitivity and specificity of skin thickness detection by high-frequecy ultrasound were evaluated by using receiver operating characteristic (ROC) curve analysis.Results Total thickness of skin (TST) of patientswith SSc were positively correlated to the total mRss (r=0.416,P=0.020) and DAI (r=0.436,P=0.014).The skin thickness of patients with mRss 0,1,2 was higher than CNT [1.45(0.60),1.70(0.30) mm,1.60 (0.30) mm vs 1.30 (0.35) mm,Z=-3.242,-6.577,-5.090,P＜0.01].The cut-off value of TST used as the evaluation of skin change was 7.4 mm by ROC curve analysis,and the sensitivity and specificity of them was 77.40％ and 87.10％ respectively,and patients with thickened skin were more likely to suffer interstitial lung disease (ILD) (16 vs 1,x2=26.004,P=0.014),higher mRss [10(6) vs 4(5),Z=-2.499,P=0.031],DAI [(5.2±2.4) vs (2.3±1.7),t=-3.104,P＜0.01)] and CRP [(8.60 (10.48) mg/L vs 3.52 (4.93) mg/L,Z=-2.276,P=0.038].Conclusion US combined with mRss are helpful to evaluate the changes of skin and disease activity of patients in SSc.US can identify the early and subclinical skin involvement that may precede mRss,providing a more reliable tool for diagnosis,treat efficacy and prediction of organ damage.
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With the rapid development and wide application of traditional Chinese medicine injection (TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the quantitative determination of potentially harmful substance 5,5'-oxydimethylenebis (2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column (150 mm × 2.1 mm, 5 µm) by gradient elution, using methanol-water containing 0.1% formic acid as mobile phase at the flow rate of 0.3 mL/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3 ng/mL and linear over the range of 0.3-30 ng/mL (=0.9998). Intra- and inter-day precision for analyte was <9.52% RSD with recoveries in the range 88.0-109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.
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Objective To comparatively analyze the domestic and foreign sicentific product, academic impact and cooperation in toxicology from 1980 to 2015.Methods The countries, Chinese scientific research institutions and authors engaged in research of toxicology were analyzed according to the InCites-covered number of published pa-pers, cited papers and collaborations .The highly cited papers covered in Web of Sciene were analyzed by biblio-metric analysis.Results The number of papers on toxicology published by USA, Britian and Japan was greater than that published by other countries.The number of papers on toxicology published by China increased significantly and their academic level was notebly improved.Conclusion China should strengthen the subject system construc-tion, attach importance to frontier and retrospective analysis and international cooperation, speed up the develop-ment of toxicology and improve the academic level of its scientific achievements .
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OBJECTIVE:To provide reference for rational drug use in respiratory department. METHODS:ADR/ADE report-ed by respiratory department of a class three grade A hospital during Jan. 2011 to Dec. 2015 from national ADR monitoring system were collected. 2011-2015 ADR/ADE database of respiratory department in a hospital was established and analyzed statistically. RE-SULTS:202 records were gotten,among which 89 cases were male(44.06%)and 113 cases were female(55.94%);the patients’ age approximated normal distribution,the incidence of ADR/ADE was the highest in 61-80 age group (55.94%);the occurrence time of ADR/ADE was mostly lower than 1 h (47.21%);the main route of administration was intravenous drip (71.29%);22 kinds of drugs were involved,and antibiotics took up the lead(43.11%);84 patients(41.58%)used 2 and more kinds of drugs before the occarrence of ADR/ADE;organs/systems involved in ADR/ADE were skin and its appendants (32.86%) and digestive system(26.19%). Most of the ADR/ADE could be cured or recovered after related treatment. CONCLUSIONS:The occurrence of ADR/ADE in respiratory department is related to various factors,of which advanced age,intravenous administration and antibiotics use are important ones. Great importance should be attached to rational clinical drug use as well as ADR/ADE monitoring and re-porting. Clinical also should pay attention to the safety of drug use in elderly patients.
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Objective To explore the role of Th17 cells in systemic lupus erythematosus (SLE)with cardiovascular disease (CVD).Methods 61 patients of SLE were collected from September 2011 to March 2013 in the Second Hospital of Hebei Medical University by revised SLE classification standards of ACR in 1997.These patients were divided two groups:22patients of SLE with CVD and 39 patients of SLE without CVD;the control group include 20 healthy.Th17 cells were measured by flow cytometry,IL-1 7 was detected by enzyme-linked immunosorbent assay.The correlation among them and the disease active index were analyzed.Results ①The percent of Th1 7 cells in the group of SLE with CVD,that in the group of SLE without CVD and that in control group were (2.09±0.98)%,(1.75±0.75)% and (0.89±0.44)%,respec-tively.The percent of Th1 7 cells in healthy group were lower than that in SLE with CVD and SLE without CVD group (t=4.717~5.030,P0.05;t=1.513,P>0.05).②The level of IL-17 were correlated positively with SLEDAI and the anti-double strand DNA (r=0.393,P=0.008;r=0.558,P<0.001),were correlated negatively with complement C3 (r=-0.423,P=0.005).The percent of Th17 cells in CD4+T cells were correlated positively with SLEDAIand the anti-double strand DNA (r=0.681,P<0.001;r=0.492,P=0.015)were correlated negatively with complement C3 (r=-0.534,P=0.027).Con-clusion The level of Th1 7 cells and IL-1 7 were high in SLE,and they were related with the disease activity.The cardiovas-cular factor had not affect the expression of Th1 7 cells and IL-1 7 in SLE.
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Objective To explore the relationship between the gait behavior changes and cognitive function in APP/PS1 transgenic mice .Methods 16 APP/PS1 transgenic mice were divided into model group and Huperzine A group, C57/BL6J mice with the same age were chosed as control group .After a 150 days consecutive treatment , Morris water maze(MWM) was used to detect the learning and memory ability and Gait analysis system (GAS-2) was used to detect the gait behavior after the treatment when the mice were 8-month-old.Results The escape latency of the model group was significantly higher than that of the control group ( P <0.05 ) , the time spended in the target quadrant , swimming distance in the target quadrant significantly lower than that of the control group ( P <0.05 ) , the first time passing through the platform prolonged significantly than the control group (P <0.05), and the number of passing though the platform reduced significantly than the control group (P <0.05).In the gait behavior experiments , compared with the control group, the average walking speed of the model group reduced significantly (P <0.05), the average walking cycle, the absolute average body angle and lateral movement increased significantly (P <0.05);The percentage of support time in a walking cycle of the left and right foot increased significantly (P <0.05).Accordingly, the percentage of swing time in a walking cycle of the left and right foot reduced significantly (P <0.05).The propulsion index of the left hand , right hand, right foot increased significantly ( P <0.05), and then the braking index of the above three feet decreased significantly ( P <0.05) .Huperzine A can improve the cognitive function , rectify the changes in the gait behavior .The two behavioral relevance shows that cognitive function and the front two feet braking , propulsion index have a high correlation index (correlation coefficients were -0.433, -0.379, P values were 0.039,0.079), the others were not. Conclusion APP/PS1 transgenic mice of 8-months-old have a remarkable impairment of learning and memory ability and disorder of gait behavior , and these two behaviors have a correlation in some extent .
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Objective This study was designed to investigate the expression of T regulatory cells (Treg) in the peripheral blood and salivary gland of patients with primary Sj(o)gren's syndrome (pSS).Methods The expression of Treg was measured by flow-cytometry analysis in 23 pSS patients and 15 healthy controls.CD4 positive cells were sorted by immunomagnetic beads,Forkhead box protein P3 (Foxp3) mRNA was extracted,real time polymerase chain reaction (RT-PCR) was used to measure Foxp3 mRNA.For the study of salivary gland,five primary billary cirrhosis (PBC) patients without pSS were selected as the control group,the expression of CD4+T cells and Foxp3+ T cells in salivary gland was examined by immunohistochemistry.The result was analyzed by t test.Results The expression of Treg in the peripheral blood of pSS patients [(5±6)％] was lower than healthy controls [(10±5)％] (t=2.190,P=0.036).There was no significant difference in Foxp3-mRNA expression between pSS patients (0.08±0.05) and controls(0.09±0.03 ) (t=0.695,P＞0.05 ).The expression of CD4+ T cells [ ( 30± 10 )％ ] and Foxp3+ T cells [ ( 10.7±5.8 ) ％ ] in the salivary gland of pSS patients increased significantly when compared with PBC control group [CD4+T (11±6)％ and Foxp3+T(3.2+1.1)％ ] (t=4.072,2.840; P＜0.05).Conclusion For pSS patients,the expression of Treg decreases in the peripheral blood,but Treg increases in the salivary gland.The results of this study suggest that Foxp3plays an important role in the pathogenesis of pSS.
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ObjectiveTo examine the clinical features of fractures and related risk factors in patients with rheumatoid arthritis(RA) in China.MethodsSix hundred and eighty-one RA patients were randomly selected from department of rheumatology of 18 hospitals of China.Data were obtained from the questionnaire,including age,sex,disease duration,the involvement of joints,treatment regimen,features of fractures etc.The possible risk factors of fracture in patients with RA were analyzed with a multi-variate Logistic regression analysis.Results① In 681 RA patients of the survey,48 patients had 54 fractures,and the incidence of fractures was about 8％.② Fractures occurred at various sites.Foot/ankle,femur,spine and wrist were the mostfrequent sites.③ The Logistic regression analysis showed that several factors increased the risk of fracture in RA patients,including long disease duration (OR:1.245,95％CI:0.987-1.570,P=0.065),male gender(OR:0.433,95％CI:0.199-0.942,P=0.035),more deformed joints(OR:1.042,95％CI:1.006-1.079,P=0.023),family history of RA (OR:2.201,95％CI:0.984-4.923,P=0.055),and high scores of SF-36(OR:1.017,95％CI:1.002-1.033,P=0.028).④ According to the degree of correlation from strong to weak,the risk factors of fracture were disease duration,SF-36,sex,number of deformed joints and family history of rheumatoid arthritis.ConclusionThe incidence of fracture is high in patients with rheumatoid arthritis.Several factors could increase the risk of fractures in RA patients,including long disease duration,male gender,more deformed joints,and family history of RA.In order to prevent the occurrence of fractures,cautions should be taken to prevent the development of fractures and treat the disease aggressively to suppress the disease activity of RA.
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<p><b>OBJECTIVE</b>1-Bromo-3-chloro-5,5-dimethylhydantoin (BCDMH) is a solid oxidizing biocide for water disinfection. The objective of this study was to investigate the toxic effect of BCDMH on zebrafish.</p><p><b>METHODS</b>The developmental toxicity of BCDMH on zebrafish embryos and the dose-effect relationship was determined. The effect of BCDMH exposure on histopathology and tissue antioxidant activity of adult zebrafish were observed over time.</p><p><b>RESULTS</b>Exposure to 4 mg/L BCDMH post-fertilization was sufficient to induce a number of developmental malformations, such as edema, axial malformations, and reductions in heart rate and hatching rate. The no observable effects concentration of BCDMH on zebrafish embryo was 0.5 mg/L. After 96 h exposure, the 50% lethal concentration (95% confidence interval (CI)) of BCDMH on zebrafish embryo was 8.10 mg/L (6.15-11.16 mg/L). The 50% inhibitory concentration (95% CI) of BCDMH on hatching rate was 7.37 mg/L (6.33-8.35 mg/L). Histopathology showed two types of responses induced by BCDMH, defensive and compensatory. The extreme responses were marked hyperplasia of the gill epithelium with lamellar fusion and epidermal peeling. The histopathologic changes in the gills after 10 days exposure were accompanied by significantly higher catalase activity and lipid peroxidation.</p><p><b>CONCLUSION</b>These results have important implications for studies on the toxicity and use of BCDMH and its analogs.</p>
Subject(s)
Animals , Antioxidants , Metabolism , Disinfectants , Toxicity , Dose-Response Relationship, Drug , Embryo, Nonmammalian , Hydantoins , Toxicity , Time Factors , Water , Chemistry , Water Pollutants, Chemical , Toxicity , ZebrafishABSTRACT
The Escherichia coli (E.coli) strain from intestinal tract of died newborn swine was isolated and cultured.Preliminary identification of the isolated strain was conducted by conventional biochemical tests,and the molecular biology detections of toxicity gene and typing gene were completed by multi-PCR.Stable toxin and heat-labile enterotoxin genes of E.coli were detected from the isolated strain.By amplifying and sequencing bacterial 16s rDNA and fliC gene,the isolated strain was identified as H10 by Blast analysis.The homology of strain H10 was 99% with bacterial 16s rDNA gene and 98% with fliC gene.
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Objective:To investigate the expression of HIF-1 and VEGF and the correlation with pathological score of synovium in adjuvant-induce-arthritis rat knee joint.Methods: Models of adjuvant arthritis(AA)in rats were made successfully, the arthral pathological score was calculated, production of HIF-1α and VEGF protein was assayed by histoimmunchemical staining at different stage after CFA inoculation.Results:The HIF-1α and VEGF concentration in experimental group were higher than that in control group, and there was significant difference (P＜0.01).And correlation between them was significantly(P＜0.01), similar with pathological score of synovium(P＜0.01).Conclusion:HIF-1α and VEGF play important roles in the development and progression of synovium of knee joint in AA rat.The interaction of them promote development and progression of neonatal vascular in synovium.
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Objective To describe the distribution of medication costs of rheumatoid arthritis patients, and to analyze the factors that may affect the costs. Methods Data were obtained from a 12-month retrospective investigation of patients with rheumatoid arthritis (RA) across China. Department of Rheuma-tology of 18 hospitals were randomly selected. The data about their social conditions, clinical conditions, medications associated with RA such as disease-modifying antirheumatic drugs (DMARDs), non -steroidal anti -inflammtory drugs (NSAIDs), steroids, biologic agents were collected, and the costs of drugs were calculated. A non-parameter test and multivariate logistic regression analysis were performed. Results Six hundred and forty six patients were enrolled into the study, 435 completed data were chosen for analysis. The results demonstrated that the average costs per patient for medications in the past year was 8018 . The total medication costs were further subdivided into the following parts: DMARDs, (represented 20% of the total costs), biologic drugs (49%), NSAIDs (4%), herbal drugs (22%), steroids (1%). Data analysis showed that patients with higher education and higher incomes, with medical insurance,better health function status and outpatients paid more on DMARDs. Extra-articular manifestations increased the odds of the high-cost group (OR: 2.180, 95%CI: 1.335～3.558, P=0.002), while poor health function status increased the probability of paying high costs (OR: 1.373, 95%CI: 1.012～1.863, P=0.041). Conclusion High medication costs in RA do exist in RA patients. The costs of medication is associated with health function status and the presence of extra-articular manifestations.
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Objective:To investigate the expression of HIF-1? and VEGF and the correlation with pathological score of synovium in adjuvant-induce-arthritis rat knee joint.Methods:Models of adjuvant arthritis(AA) in rats were made successfully,the arthral pathological score was calculated,production of HIF-1? and VEGF protein was assayed by histoimmunochemical staining at different stage after CFA inoculation.Results:The HIF-1? and VEGF concentration in experimental group were higher than that in control group,and there was significant difference(P