目的 探讨青壮年活动期强直性脊柱炎(AS)骨代谢类型与骨密度之间的关系,为临床青壮年AS骨密度下降者的预防及治疗提供依据.方法 纳入2015年2月-2020年11月在浙江省人民医院就诊的AS患者103例,分析不同骨代谢类型与骨密度的相关性.结果 入组的103例AS患者,骨密度正常组49例,骨密度低下组54例.骨密度低下组患者Ⅰ型胶原羧基端肽β特殊序列(β-CTX)、N端骨钙素(OC)、总Ⅰ型胶原氨基端前肽(P1NP)的均值均显著高于骨密度正常组(均P＜0.001).骨密度低下组又分为低中转换组(28例)和高转换组(26例).高转换组的股骨颈骨密度T值为-1.56±0.82,显著性低于中低转换组(-1.01±0.92,P=0.029).2组腰椎的骨密度T值比较差异无统计学意义(P=0.080).对于不同骨代谢类型治疗前后比较发现:在中低转换组,治疗后股骨颈骨密度值[(0.92±0.09)g/cm2]较治疗前[(0.89±0.08)g/cm2]显著改善(P=0.022);而在高转换组,治疗后股骨颈骨密度值较治疗前差异无统计学意义(P=0.080).结论 青壮年AS骨密度下降患者血清β-CTX、OC、P1NP明显升高,表现为高转换骨丢失;中低转换的骨密度下降患者通过积极基础病炎症控制,骨密度可以得到有效提升;但是,高转换骨密度下降患者治疗后骨量无显著提升,应探索更为有效的治疗方案.

目的 探讨益肾蠲痹法含药血清对骨代谢信号通路的影响.方法 正常SD大鼠随机分为对照组和益肾蠲痹组,分别经生理盐水和益肾蠲痹汤灌胃给药,获取含药血清;分离大鼠成骨细胞和破骨细胞,利用碱性磷酸酶和Van kossa染色鉴定成骨细胞,TRAP和甲苯胺蓝染色鉴定破骨细胞;将成骨和破骨细胞各分为4组:对照组、益肾蠲痹法含药血清低、中和高浓度组;通过免疫印迹检测成骨细胞骨保护蛋白(OPG)、核因子κB受体活化因子配体(RANKL)和破骨细胞核因子κB受体活化因子(RANK)的表达.结果 低、中、高浓度含药血清诱导成骨细胞OPG的表达分别为对照组的97％ (P =0.710)、122％ (P =0.005)和155％ (P ＜0.001),RANKL表达分别为对照组的81％ (P ＜0.001)、63％ (P ＜0.001)和53％ (P＜0.001),表明OPG和RANKL表达与含药血清浓度分别呈正、负相关;含药血清使破骨细胞RANK表达分别调节对照组的75％(P＜0.001)、50％(P＜0.001)和46％(P＜0.001),表明RANK表达与含药血清剂量呈负相关.结论 益肾蠲痹法含药血清通过调节OPG/RANKL/RANK信号轴可能在抗骨丢失过程中发挥作用.

Objective: beta-lactoglobulin (beta-Lg) allergy in dietary milk seriously affects the use of high-quality milk protein in infants. In order to solve this problem, the expression of miRNA and Th17 cells in milk beta-Lg allergic reaction of children's diet was studied. Method: female BALB/c mice aged 5-6 weeks were selected as the subjects and randomly divided into blank group and beta-Lg sensitized group, with 10 mice in each group. On the 1st, 7th and 14th day, the mice in the beta-Lg sensitized group were intraperitoneally injected with allergen (Freund's adjuvant + beta-Lg). Mice in the blank group were given the same amount of normal saline. Blood samples were collected from the eyeballs of mice to determine the number of inflammatory cells. The contents of Th17 related cytokines and transcription factors in spleen were detected by RT-PCR. Results: 1. the number of eosinophils and neutrophils in the beta-Lg sensitized group were 15.76/mL and 24.36/mL, respectively, which were significantly higher than those in the blank group (P < 0.05); 2. in the mice of beta-Lg sensitized group, the expression of miR-146a and miR-155 was abnormal, the number of Th17 cells was abnormally increased, and the expression levels of IL-17 and ROR gamma t were significantly increased; 3. the abnormal expression of miR-146a and miR-155 in the mice of beta-Lg sensitized group was positively correlated with the secretion of Th17 related cytokines, which could be used as one of the biological indexes to evaluate allergic reaction. Conclusion: the number of Thl7 increased abnormally in dietary milk allergy patients. miRNA gene expression and IL-17 expression could be used as one of the biological indicators to evaluate the allergic reaction of beta-Lg. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

干燥综合征(sj(o)gren syndrome,SS)是一种病因和发病机制未明,以侵犯外分泌腺,尤其是唾液腺及泪腺为主的慢性全身性自身免疫性疾病.口、眼干燥为其常见症状,但也可伴有内脏损害并出现多种临床表现[1].当累及内脏或其他系统时,具有起病隐匿、临床表现复杂的特点,极容易漏诊或误诊,延误治疗时机[2].干燥综合征累及膀胱并发直立性低血压者较为罕见,现报道1例.

结节性多动脉炎(polyarteritis?nodosa,PAN)作为一种自身免疫性疾病,目前为止发病原因尚不明确,可能与病毒感染、药物、血清过敏等相关.此病易伴多脏器受累,常累及肺、肾、脑,其中肾脏是本病最主要靶器官之一, 80%~90%患者有不同程度肾损害,临床症状常见有发热、乏力、肌肉酸痛、四肢及躯干青斑等,其临床症状不典型,易漏诊和误诊,贻误病情诊治.本文报道结节性多动脉炎并发双肾多发动脉瘤破裂出血1例.

IgG4相关性疾病(IgG4- RD)的特点是免疫介导的纤维炎症过程几乎影响所有器官,携带IgG4+的浆细胞浸润.现报道IgG4- RD患者1例的诊疗过程.

Objective To study the correlations among disease activity and cytokines and blood lipids in patients with ankylosing spondylitis(AS). Methods A total of 115 AS patients were enrolled. CRP,ESR,TG,TC,HDL-C,LDL-C,apoAI,LP(a),IL-6,IL-10 and other targets were measured,and the correlations between the levels of cytokines,blood lipid and AS were analyzed. Results TC,HDL-C and apoAI in 115 patients with AS were negatively correlated with ESR. TC,HDL-C and apoAI were also negatively correlated with CRP. At the same time,IL-6 was negatively correlated with HDL-C and apoAI. However,when IL-6 was controlled,there was no significant correlation between ESR and HDL-C(P>0.05). In addition, when apoAI was controlled,there was no significant correlation between ESR and HDL-C(P>0.05),and when HDL-C was controlled,ESR was still negatively correlated with apoAI(r=0.-308,P=0.001). When controlled IL-6,ESR was positively correlated with LP(a)(r=0.349,P<0.001). Conclusion The inflammatory state of AS patients may affect the level of apoAI through the change of IL-6 level,and then lead to the change of HDL-C level. After excluding the influence of IL-6,the level of inflammation in AS patients is still significantly correlated with LP(a).

Objective To detect the serum concentrations of interleukin-6 (IL-6) in patients with polymyositis (PM),and to explore its clinical relationships in order to investigate the pathogenesis and treatment of PM.Methods Thirty-six patients with polymyositis were enrolled from April,2010 to January,2014 in our study.Serum IL-6 and TNF-α were detected using a commercially available EILSA.The statistical differences between groups were evaluated by the analysis of variance (ANOVA).The Spearman's correlation test was used to evaluate the relationship of IL-6 and clinical and laboratory data.Results Serum IL-6 concentrations were (19.67 ± 7.16) pg/ml in active PM patients,and (15.81 ± 4.00) pg/ ml in remission,which were significantly higher thin those of controls [(8.14 ± 3.71)pg/ml,P ＜ 0.001].Furthermore,IL-6 concentrations in active PM patients were significantly higher than those in remission (P =0.043).TNFαconcentrations were (114.44 ± 36.04) pg/ml in active PM patients,and (97.65 ± 30.78) pg/ml in remission,which were significantly higher than those of controls [(55.43 ± 22.83) pg/ml,P ＜ 0.001].However,there was no significant deference between PM patients in active phase and in remission.The serum IL-6 levels were positively correlated TNF-α (r =0.709,P =0.000),and negatively correlated with current glucocorticoid dose (r =-0.573,P =0.000).Conclusion IL-6 could be used as a marker of hormone dosage when evaluating and treating PM disease.

Objective To elucidate the clinical significance of macrophage migration inhibitory factor (MIF) serum concentration in patients with polymyositis. Methods Thirty-six patients with polymyositis were enrolled. Serum samples were obtained and stored to detect MIF and interleukin (IL)-6 using commercially available enzyme-linked immunosorbent assay kits. The relationships between these cytokines and clinical data were analyzed. Results The serum MIF concentration was significantly lower in patients in remission (34.74 ± 17.75) and in healthy controls (38.87 ± 9.30 ng/ml) than that in patients with active polymyositis (50.04 ± 23.84 ng/ml). There were no significant differences between healthy controls and patients in remission. The serum IL-6 concentration in patients with active polymyositis (19.67 ± 7.16 pg/ml) was significantly higher than that in patients in remission (15.81 ± 4.00 pg/ml) and controls (8.14 ± 3.71 pg/ml). The serum IL-6 concentration was negatively correlated with the serum MIF concentration (r = −0.283). No relationship was found between the serum MIF concentration and glucocorticoid dose. The MIF concentration peaked twice during treatment when the creatine kinase concentration was decreasing. Conclusion MIF and IL-6 play important roles in the inflammation associated with polymyositis. MIF might also be involved in the early stage of regeneration in polymyositis. MIF may thus serve as a biomarker of disease activity and outcome.

目的 通过研究益肾蠲痹汤的含药血清对大鼠成骨细胞、破骨细胞增殖的影响,评价益肾蠲痹法对强直性脊柱炎骨代谢异常的治疗作用.方法 SD正常大鼠(SPF级)经灌胃给药益肾蠲痹汤,收集大鼠含药血清.分离大鼠成骨细胞和破骨细胞,通过Van kossa染色和碱性磷酸酶染色鉴定成骨细胞,TRAP染色、甲苯胺蓝染色鉴定破骨细胞.将体外培养的成骨细胞和破骨细胞,分别分为6组:空白对照组,益肾蠲痹汤大、中、小剂量含药血清组,双氯芬酸对照组和阿仑膦酸盐对照组.使用CCK-8法测定成骨细胞、破骨细胞的生长曲线,收集并测定成骨细胞培养液上清碱性磷酸酶活性.结果 含有益肾蠲痹汤药物的血清加入体外培养成骨细胞后,成骨细胞的生长曲线呈明显上升趋势,加药后细胞培养上清中碱性磷酸酶浓度增加,提示成骨细胞分泌碱性磷酸酶活性增强.生长曲线上升趋势及分泌碱性磷酸酶活性随含药血清浓度增加而作用增强.体外培养破骨细胞加入益肾蠲痹汤含药血清后,细胞增殖曲线呈下降趋势,曲线下降趋势亦随含药血清浓度升高而幅度增大.结论 益肾蠲痹汤具有促进成骨细胞增殖及提高成骨细胞活性,同时,对破骨细胞增殖有抑制作用,作用强度随药物浓度增加而增强.因此,预期益肾蠲痹汤对强直性脊柱炎骨代谢异常具有治疗作用.

Previous studies suggested a pathological role for the death decoy receptor 3 (DcR3) in systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). Herein, the expression of DcR3 in primary Sjögren’s syndrome (pSS) and the relationship with clinical characteristics were investigated. The serum DcR3 levels of pSS patients and healthy controls were measured by ELISA. Pearson’s correlation analysis was used to evaluate the relationship between the DcR3 levels with the clinical characterstics of pSS patients. Additionally, the DcR3 expression in salivary glands of pSS patients was investigated by the immunohistochemistry method. The serum DcR3 expression in pSS patients was significantly higher than healthy controls (p < 0.001), especially in new onset pSS patients (p = 0.036). Moreover, Pearson’s correlation analysis show that DcR3 levels were positively correlated with age (p = 0.013), platelet (PLT) (p = 0.002), hemoglobin (Hb) (p = 0.004), Sjögren’s syndrome disease damage activity index (SSDAI) score (p = 0.005), Sjögren’s syndrome disease damage index (SSDDI) score (p < 0.001) and EULAR Sjögren’s syndrome disease activity index (ESSDAI) score (p = 0.010). Furthermore, the DcR3 levels were significantly lower when the pSS patients were treated with the disease-modifying anti-rheumatic drugs. At last, DcR3 expression in salivary glands of pSS patients was significantly higher than healthy controls. The DcR3 expression was significantly elevated in the pSS patients and positively correlated with the clinical characteristics, and it might be an important factor involved in the progression of pSS patients and could be a potential therapeutic target.

Objectives: To investigate the effect of treatment of ankylosing spondylitis(AS) with Yishen Jianbi.Methods: 162 patients with AS were randomly divided into two groups: the treatment group with 98 patients and the control group with 64 patients.Patients in the treatment group were treated both regular medicine and Yishen Jianbi,then Compared the Bath index,ESR(erythrocyte sedimentation rate),CRP(C-neactveprotein),and BMD(bone mineral density) value between the initial status and 6 months later after the treatment.And after that,we compare those value differences after 1 year follow-up visit and 2 years follow-up visit respectively.Results: 6 months after treatment began,Bath ankylosing spondylitis disease activity index(BASDAI),Bath ankylosing spondylitis function index(BASFI),ESR and CRP in the treatment group were significantly decreased,and had a statistical significance compared with the control group(P0.05) After observed 1 year and 2 years,Bath ankylosing spondylitis measurement index(BASMI) was decreased and BMD was improved in the treatment group compared with the control group.Both them had a statistical significance compared with the control group(P0.05).We found the more differences in efficacy with the time.Conclusion: Yishen Jianbi has an exact curative effect on AS patients.The short term effect are the anti-inflammatory while long term express as improving the bone metabolism and preventing spinal column and arthrosis from ankylosing.

INTRODUCTION:Glucocorticoid (GC) therapy remains important in improving the prognosis of patients with systemic lupus erythematosus (SLE). However, some patients do not achieve an effective response with GC treatment, creating an obstacle to the remission of SLE. Identification of the underlying mechanisms responsible for steroid resistance can be significant. Macrophage migration inhibitory factor (MIF) arouses our interest because of its reciprocal relationship with GCs. In the present study, we investigated for the first time whether MIF correlated with steroid resistance in SLE and explored potential mechanisms of action.METHODS:Sixty-two patients with SLE (40 steroid sensitive and 22 steroid resistant) and 21 normal controls were recruited. Serum levels of MIF were measured by ELISA. Cytosolic MIF and IκB expression in peripheral blood mononuclear cells (PBMCs) were determined by western blotting. The electrophoretic mobility shift assay was assessed by NF-κB in nuclear aliquots. Gene silencing was applied to reduce expression of MIF in PBMCs in steroid-resistant patients. PBMCs obtained from steroid-sensitive patients were treated with recombinant human MIF of different concentrations.RESULTS:MIF levels in serum and PBMCs were higher in steroid-resistant patients compared with steroid-sensitive patients and controls. In contrast to the steroid-sensitive group, NF-κB levels were significantly higher and IκB levels lower in steroid-resistant patients. After MIF gene silencing, IκB levels in cells from steroid-resistant patients were increased. In steroid-sensitive patients, a decrease in IκB levels and an increase in NF-κB expression from baseline were detected in PBMCs treated with a higher concentration of recombinant human MIF. Treatment with recombinant human MIF did not regulate expression of IκB and NF-κB in PBMCs from patients treated with an anti-MIF monoclonal antibody.CONCLUSIONS:Our results indicated that MIF may play a role in the formation of steroid resistance in SLE by affecting the NF-κB/IκB signaling cascade. As a regulator of glucocorticoid sensitivity, MIF may be a potential target for steroid sparing.

The objective of this study is to describe the interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients of China, and to study clinical significance of high-resolution computed tomography (HRCT) in evaluation and treatment. One hundred and ten Chinese patients (79 women and 31 man) diagnosed with RA between December 2008 to November 2009 were analyzed. According to the HRCT, 47 (42.73%) RA patients were diagnosed as ILD. Old age, smoking and pulmonary rales were closely related to ILD (P < 0.05). The main appearances of ILD were ground-glass (39.09%), honeycombing (4.55%), reticular patterns and consolidation (1.82%). Patients with reticular patterns and honeycombing were more likely to show the respiratory symptoms. It was also common to find other abnormal changes, such as fiber cord shadow (22.73%), lung markings fuzzy disorder (30%), pulmonary nodules (11.82%), emphysema (9.09%), bronchiectasis (3.64%), subpleural nodules (11.82%) and pleural thickening (24.55%). In treatment, honeycombing and subpleural nodules were more common in patients with methotrexate (MTX) and/or leflunomide treatment than without (P < 0.05). Other abnormal changes were no statistical significance (P > 0.05). Pulmonary involvement is common in RA patients, and it is suggested that HRCT could be a sensitive and useful way in evaluating the lung of RA patients.

目的 探讨强直性脊柱炎(AS)患者的骨丢失特点及相关因素.方法 收集156例AS确诊患者,测定患者Bath指数、血沉(ESR)、C反应蛋白(CRP)、骨密度、血清骨源性碱性磷酸酶(BAP)、抗酒石酸酸性磷酸酶5b(TRAP5b)及1,25-(HO)2VitD3浓度,分析骨代谢指标变化特点及与临床指标相关性.结果 AS患者的血清TRAP5b较正常组增高(P＜0.05),1,25-(HO)2VitD3浓度和BAP水平与正常组的差异均无统计学意义(均P ＞0.05).骨密度测定显示:骨质疏松、骨量减少和骨量正常者分别为49、51、56例,骨质疏松组ESR、CRP、TRAP5b均高于骨量减少和骨量正常组(P＜0.05或0.01);骨质疏松组的Bath疾病活动指数(BASDAI)、BAP均较正常组增高 (均P＜0.05),Bath功能指数(BASFI)较骨量减少组增高(P＜0.05).TRAP5b与CRP、BASFI、BASDAI呈正相关(均P＜0.05). 结论 AS患者普遍存在骨代谢异常,表现为高转换骨丢失,并与CRP、BASDAI、BASFI呈正相关,提示骨丢失是AS病情活动的临床表现之一.

类风湿性关节炎(RA)是一种以对称性、多个外周小关节累及为主要临床表现的风湿性疾病.然而有研究发现,约50%的RA患者可表现为不同程度的关节外系统的累及,其中肺部累及较为常见,成为影响RA患者生存率的重要因素之一[1].现笔者对近年来收治的RA患者肺部高分辨率CT(HRCT)的表现进行了回顾性分析,以期为临床诊疗提供帮助.

干燥综合征(Sj(o)gren's syndrome,SS)是一种以侵犯泪腺、唾液腺等外分泌腺为主的慢性自身免疫性疾病.我国人群患病率为0.3%～0.7%,是自身免疫性疾病中极为常见的一种,但其临床研究远落后于系统性红斑狼疮(SLE)、类风湿关节炎(RA)等其他风湿性疾病[1],故对病因形成及临床特征进行探析性研究,为加强疾病的早期诊断和治疗非常必要。

OBJECTIVE:To describe the onset, clinical features, prognostic factors, and treatment of adult-onset Still's disease (AOSD) in cases from China.METHODS:Sixty-one Chinese patients with AOSD were analyzed retrospectively.RESULTS:Common clinical features were fever (100.0%), rash (88.5%), and arthritis (82.0%). The laboratory findings were as follows: leukocytosis (83.6%), increased erythrocyte sedimentation rate (100.0%), elevated transaminase concentrations (23.0%), elevated ferritin levels (79.6%), negative antinuclear antibody (88.5%), and negative rheumatoid factor (88.5%). Of the 61 patients, 44.3% exhibited a monocyclic disease pattern, 29.5% experienced disease relapse at least once, 16.4% exhibited chronic articular course, and 9.8% died; most deaths were due to pulmonary infection and respiratory failure. Based on the disease course, we divided the 61 patients into 2 groups: those with favorable outcome (cyclic disease course, n = 45) and unfavorable outcome (chronic disease course or death, n = 16). We analyzed the prognostic factors for the 2 groups, and found that pleuritis, interstitial pneumonia, elevated ferritin levels, and failure of fever to subside after 3 days of prednisolone at 1 mg/kg/day were unfavorable prognostic factors for patients with AOSD.CONCLUSION:Patients with AOSD had complex symptoms with no specific laboratory findings. Our results indicate that AOSD is not a relatively benign disease, especially in cases that are refractory to high doses of prednisone.

Objectives:To investigate the effect of treatment of ankylosing spondylitis(AS) with Yishen Juanbi pill.Methods:105 patients with AS were randomly divided into two groups:the treatment group with 64 patients and the control group with 41 patients.Patients in the control group were treated with regular medicine,and Yishen Juanbi pill was added to the treatment group.The Bath index,erythrocyte sedimentation rate(ESR),C-neactveprotein(CRP) were tested before the treatment began and 3 months later,and BMD(bone mineral density) were measured before the treatment began and 6 months later.Results:3 months after treatment began,Bath ankylosing spondylitis disease activity index(BASDAI),Bath ankylosing spondylitis function index(BASFI),ESR and CRP in the treatment group were significantly decreased,and had a statistical significance compared with the control group(P0.05).There also a larger reduction of Bath ankylosing spondylitis measurement index(BASMI) in the treatment group compared with the control group,but there was no statistical significance(P0.05).The incidence of lumbar BMD reduction in AS patients is 56.7%.There was significant improvement of the lumbar BMD reduction in the treatment group(P0.05).Conclusion:Yishen Juanbi pill has an exact curative effect on AS patients.The effect mechanism is the significant anti-inflammatory and analgesic effect and reducing spinal bone loss.

To detect the auto-antibodies against ATP-binding cassette transporter A1(ABCA1)in serum samples of patients with systemic lupus erythematosis(SLE) and to explore its significance in the pathogenesis of atherosclerosis in these patients,the auto-antibodies against ABCA1 in sera of 75 SLE patients and 38 healthy individuals were detected by immunoblotting assay,and the effect of the anti-ABCA1 antibody IgG on the efflux of cholesterol from THP-1 cells was examined. It was demonstrated that the anti-ABCA1 antibody could be detected in sera of SLE patients with a positive rate of the antibody detection of 29.3%,however,none was detected in healthy controls(P0.05). The positive rate of the autoantibody detection in SLE patients with plagues was higher than that of patients without plaques(43 8% vs 16 3%,P0.05). In addition,the purified anti-BACA1 antibody IgG could inhibit the efflux of cholesterol from THP-1 cells in vitro,with a inhibition rate of 28.7% and a significant difference with those of IgG in healthy individuals. It is evident from these observations that the findings demonstrated in the present study may be related to the development of atherosclerosis in SLE patients.