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ObjectiveTo evaluate the effect of Astragali Radix （AR）-Angelicae Sinensis Radix （ASR） drug pair on supplementing Qi and activating blood circulation in rats with Qi deficiency and blood stasis and provide a theoretical basis for clinical rational medication and identification and quality control of compound pharmacodynamic substances from the three aspects of characteristic map， identification of pharmacodynamic substances， and comparison of blood components. MethodHigh-performance liquid chromatography （HPLC） was employed to establish the fingerprint of AR∶ASR （3∶1）， and ultra-high performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry （UPLC-Q-Exactive Orbitrap-MS） was employed to analyze the ingredients of the decoction. Adult male Wistar rats with SPF grades were selected and randomly divided into a blank group， a model group， a 3∶1 group， and a 5∶1 group. The rat model of Qi deficiency and blood stasis syndrome was prepared by controlling food intake and swimming in cold water every day. In parallel， each group was given medicine （or water） once a day. The dose of drug groups was 10.2 g∙kg-1， and the model group and blank group were given the same amount of distilled water for 15 d. Animal behavior， body weight， whole blood and plasma viscosity， thymus index， spleen index， the levels of adenosine triphosphate （ATP）， adenosine diphosphate（ADP）， von willebrand factor （vWF）， and ATP/ADP value in serum of rats were recorded. The morphology of vascular endothelium was observed by hematoxylin-eosin （HE） staining and scanning electron microscopy. UPLC-Q-Exactive Orbitrap-MS was used to analyze prototype and metabolic components in serum. ResultThe fingerprint of AR-ASR drug pair （AR-ASR 3∶1） was established. UPLC-Q-Exactive Orbitrap MS identified 49 chemical components in vitro and preliminarily identified 11 prototype components absorbed into blood in vivo. As compared with the blank group， the body mass decreased significantly （P<0.01）， the whole blood （high shear， middle shear， and low shear） viscosity and plasma viscosity were significantly increased （P<0.05， P<0.01）， the thymus index and spleen index decreased significantly （P<0.05， P<0.01）， serum ATP content decreased significantly （P<0.01）， ADP content increased significantly （P<0.01）， ATP/ADP value decreased significantly （P<0.01）， and vWF content increased significantly （P<0.01）. The results of HE staining and scanning electron microscopy showed that the vessels were partially damaged， showing the structural disorder of the intima， the bulge， defect， and roughness of the endothelium， and the obvious cell adhesion and migration in the model group. As compared with the model group， the body mass also increased significantly （P<0.01）. The results of whole blood and plasma viscosity showed that the whole blood low shear viscosity was significantly decreased in the 3∶1 group （P<0.05）. The results of thymus index and spleen index showed that 5∶1 group significantly increased the thymus index of rats （P<0.05）. The results of serum ATP and ADP levels showed that the 5∶1 group had more significant effects on ATP and ADP levels （P<0.05）， and both groups significantly reduced ATP/ADP values （P<0.01）. The results of serum vWF level showed that the vWF content in the 3∶1 group decreased significantly （P<0.05）. The results of HE staining and scanning electronic microscopy showed that the damage of vascular endothelium was improved in the treatment group and the structure of intima was neat. ConclusionAR-ASR drug pair can improve the macro and micro indexes of rats with qi deficiency and blood stasis in the 3∶1 and 5∶1 groups. Overall， the 5∶1 ratio has a better effect on supplementing Qi but 3∶1 ratio has a better effect on promoting blood circulation.
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BACKGROUND@#Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.@*METHODS@#The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months.@*RESULTS@#Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group.@*CONCLUSION@#Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR2000039799.
Subject(s)
Humans , Quality of Life , China , Arthritis, Rheumatoid/drug therapy , Piperidines/therapeutic use , Treatment Outcome , Antirheumatic Agents/therapeutic use , Pyrroles/therapeutic useABSTRACT
Objective:Anti-synthase syndrome (ASS) is a rare autoimmune disease. To increase the understanding of the disease and reduce the rate of miss diagnosis.Methods:The clinical data of 8 patients with positive anti-synthase antibody afterprimary Sj?gren's syndrome (pSS) were retrospectively analyzed and descriptive statistical analysis was carried out.Results:The diagnosis of Sjogren's syndrome (SS) was in accordance with the revised European criteriaof SS issued by the US-Europe consensus Group in 2002 or the classification criteria of American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) SS in 2016, and the diagnostic ASS was in accordance with the diagnostic criteria of Conners in 2010 or Solomon in 2011. Eight(100%) patients had a history of interstitial lung disease, and 7 (88%) patients had fever (oral temperature >38.5 ℃). All patients were positive for anti-Ro-52 antibody, 4 patients were positive for anti-PL-7 antibody, 2 patients were positive for anti-EJ antibody, 1 patient was positive for both anti-PL-7 antibody and anti-EJ antibody, and 1 patient was positive for anti-PL-12.Conclusion:pSS patients with severe interstitial lung disease or high fever of unknown causes should be screened for anti-synthase antibodies and the possibility of ASS.
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Objective:To investigate the clinical manifestations, laboratory and imaging features, treatment and prognosis of systemic lupus erythematosus (SLE) with primary sclerosing cholangitis (PSC).Methods:This is a retrospective case series study describing the clinical, laboratory and imaging manife-stations, treatment and prognosis of 3 SLE patients with PSC. The related literatures were reviewed.Results:In total, 10 patients were included. SLE with PSC, with an average age of (43±17) years old, was more common with hematological and renal involvement, jaundice and arthralgia, positive anti-double-stranded DNA (anti-dsDNA) antibody, hypocomplementemia, elevated erythrocyte sedimentation rate (ESR) and abnormal liver function with predominately elevated alkaline phosphatase (ALP). The classic magnetic resonance cholangio-pancreatography (MRCP) features of PSC include multifocal strictures, beading and areas of dilatation involving the intra- and/or extrahepatic bile ducts. The treatment included glucocorticosteroids, immunosup-pressants and ursodeoxycholic acid (UDCA), and some patients required biliary drainage. Most patients had a good prognosis.Conclusion:Although PSC is rare, attention should be paid to SLE patients with abnormal liver function, especially with elevated ALP, in order to differentiate from PSC.
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Objective:To observe the clinical efficacy and adverse reactions of rituximab in the treatment of systemic sclerosis (SSc).Methods:Eight SSc patients who received rituximab treatment in the Department of Rheumatology of Shanghai Ruijin Hospital from November 2016 to May 2020 were treated with rituximab at week 0, week 2, week 4, week 24 and week 48. The clinical symptoms and laboratory parameters were evaluated at baseline, week 4, week 24 and week 48 respectively. All data were analyzed by Wilcoxon test.Results:All the patients were diagnosed as diffuse SSc, including seven females and one male, with a median disease course of 2.5 years. At week 0, week 24 and week 48, the modified Rodnon skin scores (MRss) were 16.5 (11.8, 29.5) , 14.5 (9.5, 27) ( Z=0.841) and 10.5 (7, 24.3) ( Z=0.420) respectively, which were significantly improved as compared with the baseline ( P<0.05). The patients' self-scores were 60(50, 77.5), 52.5(41.3, 67.5)( Z=0.113) and 47.5(36.3, 57.5)( Z=0.474) respectively, which were significantly improved at week 24 and week 48, and the High Resolution CT (HRCT) scores at baseline and week 48 were 2.7(1.02, 3.7) and 1.6(0.65, 2.95)( Z=0.964) respectively, significantly improved after treatment ( P<0.05). The pulmonary aterial hypertension (PAH) values were 48(41, 58.5) mmHg and 47(38.5, 57) mmHg ( Z=0.315) respectively. There was no significant difference between the two groups. Clinical observation showed that the condition was improved and no adverse reaction occurred at the same time period. Conclusion:The improvement of skin sclerosis, pulmonary interstitial lesion and pulmonary artery pressure can be observed during the treatment with rituximab, which may be a new choice for the treatment of SSc. There is no serious adverse reaction during the treatment, and the patients are well tolerated and safe.