Objective:Cardiac remodeling is a common pathological change in various cardiovascular diseases and can ultimately result in heart failure.Thus,there is an urgent need for more effective strategies to aid in cardiac protection.Our previous work found that sphingosine-1-phosphate(S1P)could ameliorate cardiac hypertrophy.In this study,we aimed to investigate whether S1P could prevent cardiac fibrosis and the associated mechanisms in cardiac remodeling.Methods:Eight-week-old male C57BL/6 mice were randomly divided into a sham,transverse aortic constriction(TAC)or a TAC+S1P treatment group.Results:We found that S1P treatment improved cardiac function in TAC mice and that the cardiac fibrosis ratio in the TAC+S1P group was significantly lower and was accompanied by a decrease in α-smooth muscle actin(α-SMA)and collagen type I(COL I)expression compared with the TAC group.We also found that one of the key S1P enzymes,sphingosine kinase 2(SphK2),which was mainly distributed in cytoblasts,was downregulated in the cardiac remodeling case and recovered after S1P treatment in vivo and in vitro.In addition,our in vitro results showed that S1P treatment activated extracellular regulated protein kinases(ERK)phosphorylation mainly through the S1P receptor 2(S1PR2)and spurred p-ERK transposition from the cytoplasm to cytoblast in H9c2 cells exposed to phenylephrine.Conclusion:These findings suggest that SphK2 and the S1PR2/ERK pathway may participate in the anti-remodeling effect of S1P on the heart.This work therefore uncovers a novel potential therapy for the prevention of cardiac remodeling.

甲襞微循环检测(nailfold videocapillaroscopy,NVC)具有无创、安全、直观、可量化、便于随访等特点.20世纪70年代,Maricq等[1]开始将NVC应用于结缔组织病(connective tissue disease,CTD).而自2013年美国风湿病学会(American College of Rheumatology,ACR)/欧洲抗风湿病联盟(European League Against Rheumatism,EULAR)将"NVC 异常"写入系统性硬化症(systemic sclerosis,SSc)分类诊断标准中以后[2],NVC逐渐成为越来越多风湿病学专家的主流检测手段之一.本文将对NVC在风湿免疫病中的应用进行综述.

目的:评估风湿病患者在新型冠状病毒肺炎(COVID-19)疫情期间应用生物制剂(包括依那西普、阿达木单抗、托法替布、巴瑞替尼、托珠单抗)的安全性,为风湿病患者在疫情爆发期间能否使用生物制剂提供临床指导.方法:通过电话随访和自制问卷的方式,对1 154名在COVID-19疫情爆发(即2019年12月)前有生物制剂使用记录的湖北省风湿病患者进行随访调查,收集患者的临床资料,包括性别、年龄、疾病诊断、病程、合并症、用药史、有无疾病复发、COVID-19暴露史、是否感染COVID-19等.结果:排除疫情期间不在湖北居住(2019年12月～2020年4月)、失访或死亡(死因非COVID-19),及停用生物制剂超过该药物五个半衰期以上的患者,湖北省共计有999例患者纳入研究.所有使用生物制剂患者均未感染COVID-19,仅1例患者在停用巴瑞替尼1个月后感染COVID-19.相较于疫情期间停用生物制剂的患者而言,使用巴瑞替尼的风湿病患者复发率较低.其他生物制剂组如托珠单抗、依那西普、阿达木单抗中,停药组和用药组的激素及抗风湿类药物(DMARDs)使用率、疾病复发率比较差异无显著统计学意义.结论:疫情期间风湿病患者使用生物制剂并不会增加感染SARS-CoV-2的风险,可持续使用生物制剂或靶向抑制剂,以降低疾病复发率及感染风险.

[This corrects the article DOI: 10.1016/S2665-9913(20)30227-7.].

Objective:To elucidate the correlation between peripheral blood levels of pentraxin 3 (PTX3) and fibroblast growth factors 2 (FGF2) and clinical manifestations, immunological indexes and disease activity of systemic lupus erythematosus (SLE) patients.Methods:The correlation between peripheral blood levels of PTX3 and FGF2 and clinical manifestations, immunological indexes and disease activity of SLE pa-tients was determined. T test, Mann-Whitney U test and Spearman's rank correlation coefficient were analyzed statistically. Results:Plasma PTX3 levels were significantly higher in SLE patients than in healthy controls (3 191±2 423) pg/ml vs (755±432) pg/ml, t=5.595, P<0.01) . The titer of PTX3 in patients with hematologic in-volvement was higher than that in the patients without [(3 810±2 840) pg/ml vs (2 493±1 830) pg/ml, t=2.008, P=0.049). Plasma PTX3 concentration in SLE patients was positively correlated not only with the level of 24 h urine protein ( r=0.498 6, P=0.005 9), but also with ESR ( r= 0.376, P=0.007) and systemic lupus erythematosus disease activity index (SLEDAI) scores ( r=0.405, P=0.003). On the contrast, plasma PTX3 concentration in SLE patients was negatively correlated with complement 3 ( r=-0.405, P=0.005). Increased serum PTX3 levels accompanied by increased serum FGF2 levels was observed. Plasma FGF2 concentration in SLE patients was positively correlated with SLEDAI scores ( r=0.326, P=0.019), but negatively correlated with level of comple-ment 3 ( r=-0.414, P=0.004) and complement 4 ( r=-0.451, P=0.007). Levels of FGF2 were higher in patients with positive anti-NuA antibody [(138±91) pg/ml vs (59±68) pg/ml, t=2.996, P=0.004 2), anti-dsDNA antibody [(120±96) pg/ml vs (56±58) pg/ml, t=3.583, P=0.000 7] and anti-rRNP antibody (151±109) pg/ml vs (63±61) pg/ml, t=3.757, P=0.000 4) than in patients with negative of these antibodies. Conclusion:The levels of PTX3 and FGF2 in peripheral blood may play a role in determining the disease activity and clinical phenotype of SLE, and can help doctors to make diagnosis and treatment decisions.

OBJECTIVE:The clinical features of rheumatic patients with coronavirus disease 2019 (COVID-19) have not been reported. This study aimed to describe the clinical features of COVID-19 in rheumatic patients and provide information for handling this situation in clinical practice.METHODS:This is a retrospective case series study. Deidentified data, including gender, age, laboratory and radiological results, symptoms, signs, and medication history, were collected from 2326 patients diagnosed with COVID-19, including 21 cases in combination with rheumatic disease, in Tongji Hospital between 13 January and 15 March 2020.RESULTS:Length of hospital stay and mortality rate were similar between rheumatic and non-rheumatic groups, while the presence of respiratory failure was more common in rheumatic cases (38% vs 10%, p<0.001). Symptoms of fever, fatigue and diarrhoea were seen in 76%, 43% and 23% of patients, respectively. There were four rheumatic patients who experienced a flare of rheumatic disease during hospital stay, with symptoms of muscle aches, back pain, joint pain or rash. While lymphocytopaenia was seen in 57% of rheumatic patients, only one patient (5%) presented with leucopenia in rheumatic cases. Rheumatic patients presented with similar radiological features of ground-glass opacity and consolidation. Patients with pre-existing interstitial lung disease showed massive fibrous stripes and crazy-paving signs at an early stage. Five rheumatic cases used hydroxychloroquine before the diagnosis of COVID-19 and none progressed to critically ill stage.CONCLUSIONS:Respiratory failure was more common in rheumatic patients infected with COVID-19. Differential diagnosis between COVID-19 and a flare of rheumatic disease should be considered.TRIAL REGISTRATION NUMBER:ChiCTR2000030795.

目的:评估新型冠状病毒肺炎(COVID-19)患者凝血及纤溶功能损伤相关因素及凝血、纤溶功能障碍对预后的影响.方法:回顾性分析263例COVID-19确诊病例,按照COVID-19诊疗方案(试行第七版)分为轻、重、危重型3组,进一步将其分为非危重型(包括轻型及重型)和危重型2组,分析2组患者的临床特征;根据患者的血清D-二聚体(D-Dimer)及纤维蛋白原降解产物(FDP)水平的正常与否,将2组患者分为D-Dimer正常与异常组及FDP正常与异常组,比较其氧合指标及炎症反应相关指标,将差异有统计学意义的指标纳入多因素logistic回归分析;按照患者是否发生死亡(本研究中死亡病例仅存于危重型患者之中)分为死亡组与存活组,分析2组患者的凝血及纤溶功能,将差异有统计学意义的指标纳入多因素logistic回归分析.结果:非危重型患者D-Dimer异常组较正常组经皮氧饱和度(SpO2)及淋巴细胞计数显著降低,C反应蛋白(CRP)、白细胞及中性粒细胞计数显著升高,白介素6(IL-6)升高患者显著增多,多因素分析结果示:随着SpO2及淋巴细胞计数升高,D-Dimer水平升高的风险降低[OR= 0.806,95％CI(0.707,0.919),P = 0.001及OR =0.09,95％CI(0.010,0.819),P = 0.033].非危重型患者FDP正常组与异常组上述指标比较结果同上,多因素分析示随着SpO2升高,FDP水平升高的风险降低[OR= 0.868,95％CI(0.768,0.979),P = 0.022].危重患者FDP异常组较正常组SpO2显著降低(P ＜0.05),FDP其余指标及D-Dimer上述指标比较,差异无统计学意义(均P＞0.05).死亡组较存活组凝血及纤溶功能异常更显著:凝血酶原时间(PT)更长、血清D-Dimer及FDP水平更高(均P ＜0.05),死亡患者与存活患者的凝血及纤溶功能多因素分析结果示,PT延长是死亡的危险因素[OR=3.372,95％CI(1.493,7.612),P=0.003].结论:入院时较低的SpO2可能导致COVID-19患者血清D-Dimer和FDP水平升高;死亡患者较存活患者凝血及纤溶功能异常更显著,PT延长可能是患者死亡的危险因素.

Many connective tissue diseases present with various extraarticular manifestations. One of these is interstitial lung disease, which should be a focus of rheumatologists and physical clinicians because of its severe complications. The current study aimed to analyze clinical manifestations of various connective tissue disease-associated interstitial lung disease (CTD-ILDs) patients, evaluating differences in the inflammatory indexes, immunological serologies, and alterations of tumor-associated biomarkers in CTD-ILDs patients. Retrospective analysis of 332 CTD-ILDs patients, enrolled from the ward of the Rheumatology Department in Tongji Hospital, from January 2005 through December 2013, was carried out. The study included idiopathic pulmonary fibrosis (IPF) patients as the positive control group. Gender composition in different CTD-ILDs was statistically different with female predominance, while IPF patients consisted of slightly more males than females. Smoking, exertional dyspnea, and coughing were more common in patients with IPF, while velcro rales were more common in patients with RA-ILD. The percentage of patients with serum AFP, CEA, and NSE levels above upper normal limits was statistically different (more proportion in PM/DM-ILD patients). A positive correlation was found between blood levels of CA125, CA199, CA724, and CYFRA21-1 and patient age in CTD-ILD patients. Differences in gender, age, ILD symptoms, and tumor-associated markers existed not only between CTD-ILDs and IPF patients, but also between different subtypes of CTD-ILD. For early diagnosis of ILD in CTD patients, precise physical examinations are required in patients with subclinical disease. Tumor biomarkers can be screened in ILD patients due to their prognostic potential.

Membrane-coated microvesicles (MVs) have been identified as important mediators in intercellular communication. During the process of apoptosis, dying cells dynamically release MVs. Neutrophils are the most abundant type of leukocytes in the circulation. Due to their very short lifespan, it is likely that they are the source of large amounts of apoptotic cell-derived MVs. Here, we show that MVs released by apoptotic human polymorphonuclear neutrophils (apoPMN-MVs), but not the apoptotic neutrophils themselves, selectively suppress the proliferation of CD25 (IL-2Rα)neg CD127 (IL-7Rα)pos Th cells in a dose-dependent manner. In contrast, the proliferation of total T cells is not affected by MVs. Importantly, apoPMN-MVs suppress the secretion of IL-2 as well as the expression of and signaling via the IL-2 receptor (IL-2R) by CD25neg CD127pos Th cells. Addition of IL-7 strongly reduced the suppression of T-cell proliferation by MVs and the addition of IL-2 completely abrogated the suppressive effect. Thus, apoPMN-MVs suppressed a subset of Th cells by downregulating IL-2 and IL-2R expression and signaling. This may represent an important mechanism to prevent the activation and expansion of resting T cells in the absence of sufficient cytokine stimulation, and thereby maintaining immune tolerance.

Objective To establish a point-scoring diagnostic system for Sjögren's syndrome (SS) based on quantified SPECT imaging of salivary gland, and evaluate its feasibility and performance compared with 2002 AECG criteria and 2012 ACR criteria. Methods 213 patients with suspected SS enrolled in this study. The related clinical data of all patients were collected. All patients were evaluated and grouped on a clinical basis and posttreatment follow-up by rheumatology specialists as the unified standard (SS group with 149 cases and nSS group with 64 cases). From SPECT imaging of salivary gland, Tmax, UImax, Ts and EFs were derived for bilateral parotid and submandibular glands, and compared between the groups. A point-scoring diagnostic system for SS was established based on the quantified SPECT imaging of salivary gland. We estimated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the new diagnostic system, compared with 2002 AECG criteria and 2012 ACR criteria. Results When 7.0 was used as the cut-off point, the sensitivity, specificity, PPV, NPV and accuracy for the new point-scoring system in diagnosing SS were 89.93% (134/149), 93.75% (60/64), 97.10% (134/138), 80.00% (60/75) and 91.08% (194/213), respectively. The new point-scoring diagnostic system based on quantified SPECT imaging of salivary gland keeps the specificity comparatively to 2002 AECG criteria and 2012 ACR criteria, but improves the sensitivity significantly (P<0.01). Conclusion The new point-scoring diagnostic system for SS based on quantified SPECT imaging of salivary gland may be superior to 2002 AECG criteria and 2012 ACR criteria, with higher sensitivity and similar specificity in the diagnosis of SS. Additionally, it also has good feasibility in the clinical settings.

BACKGROUND:Subcutaneous panniculitis-like T cell lymphoma is a very uncommon subtype of cutaneous T cell lymphoma. The manifestations of this rare disease are atypical at onset, and may mimic some rheumatic or dermatologic diseases, which causes the delay of diagnosis and treatment.CASE REPORT:We report a 24-year-old man suffering from intermittent fever and skin nodules on the left anterior chest wall, who was initially misdiagnosed with nodular panniculitis and finally diagnosed with subcutaneous panniculitis-like T cell lymphoma through repeat examination of biopsy of the skin nodule. Positron emission tomography revealed extracutaneous adipose tissue involvement. Subsequently, hemophagocytic syndrome occurred while under a conventional dose of glucocorticoid, but remission was induced by treatment with cyclosporine A and high doses of dexamethasone.CONCLUSIONS:In order to avoid the delay diagnosis and inappropriate treatment of subcutaneous panniculitis-like T cell lymphoma, in addition to a thorough physical examination, PET-CT and disease-specific pathologic, immunophenotypic, and T cell receptor tests of the skin biopsy should be performed. Extracutaneous involvement, especially hemophagocytic syndrome, indicated worse prognosis. Even so, cyclosporine A plus high-dose corticosteroid could be an option of treatment.

There are several therapeutic strategies available for the treatment of an acute gout attack and the prevention of recurrent gout flares, and they include nonsteroid anti-inflammatory drugs. This prospective study was aimed at evaluating the efficiency and safety of diacerein in combination with febuxostat on urate control, global assessments of disease activity, self-monitored gouty acute flare times, inflammatory markers, and clinical symptoms associated with their life quantity in patients with refractory gout. A total of 64 patients with refractory gout were sequentially recruited and prescribed with oral febuxostat alone or febuxostat plus diacerein daily for 12 weeks. The intensity of joint pain, numbers of acute flare, disease activity and the levels of serum amyloid A, mature IL-1β, IL-18, C-reactive protein, and urate in individual subjects were routine analyzed. In comparison with that treatment with febuxostat alone, treatment with both drugs for 12 weeks had a better therapeutic effect on reducing the values of visual analog scales, acute flares, and healthy assessment questionnaire scores in these gout patients. Furthermore, treatment with both drugs also significantly reduced the mean daily dose of etoricoxib and the levels of serum IL-1β and serum amyloid A. There was no significant difference in the frequency of patients with adverse effect between these 2 groups of patients. In conclusion, combination of diacerein and febuxostat had better therapeutic effect on reducing acute gout flares, inflammation, and clinical symptoms in patients with refractory gout.

Objective: To summarize the clinical manifestation, treatments and prognosis of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) . Methods: Clinical manifestation, imaging data, laboratory indexes, treatments and prognosis were analyzed retrospectively in 34 patients diagnosed as NPSLE. Results: Among 818 cases with SLE, 34 cases were diagnosed with NPSLE (4.16%). The most frequent initial manifestations were headache (24.2%) and cerebrovascular symptoms and signs (22.3%); fever (97.1%) and newly emerging rash (61.8%) were the most common accompanied general symptoms. According to SLEDAI score, 76.5% of NPSLE patients were in severe active stage (SLEDAI score≥15). Conclusion: The symptoms of NPSLE were heterogeneous. It was common that NPSLE present two or more clinical subtypes at the same time. Cerebral imaging examination was important for the diagnosis of NPSLE.

BACKGROUND AND OBJECTIVE:Cytochrome P450 (CYP) arachidonic acid epoxygenases promote cell proliferation and inhibit apoptosis in endothelial cells. This study was to investigate the effects of CYP epoxygenases on the proliferation of tumor cells and possible signaling pathways.METHODS:The effects of recombinant adeno-associated virus (rAAV) mediated cytochrome P450 2J2 (CYP2J2), cytochrome P450 F87V (CYPF87V) and anti-CYP2J2 on proliferation of Tca-8113, A549, Ncl-H446 and HepG2 cells were measured using MTT and flow cytometry. Expressions of phosphorylated epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK)1/2 and Akt before and after transfection were detected by western blot. Tca-8113 cells infected with rAAV-CYP2J2, rAAV-CYPF87V, rAAV-antiCYP2J2 and rAAV-GFP were inoculated into nude mice, to observe the effect of CYP epoxygenases on the growth of xenografts.RESULTS:Infection of Tca-8113, A549, Ncl-H446 and HepG2 cells with rAAV-CYP2J2 and rAAVCYPF87V significantly increased the proliferation of tumor cells by 1.7-, 1.4-, 1.6- and 2.2-fold, and 2.0-, 1.5-, 1.8- and 2.0-fold respectively, as compared with control cells. On the contrary, infection with rAAV-antiCYP2J2 inhibited the proliferation of the four tumor cell lines. Moreover, CYP epoxgenases remarkably enhanced phosphorylation of EGFR, ERK1/2 and Akt, and upregulated total PI3K by 2-, 2.3-, 2.4- and 1.9-fold in the four cell lines, while rAAV-antiCYP2J2 exerted an inhibition effect. Infection of CYP450 epoxygenase genes markedly increased the cell percentage in S/G(2)/M phases by 210% as compared to control Tca-8113 cells. rAAV-CYP2J2 and rAAV-CYPF87V promoted tumor growth of Tca-8113 cell xenografts in nude mice in comparison to the control and rAAV-antiCYP2J2 groups.CONCLUSION:CYP epoxygenases efficiently promote the proliferation of tumor cells, which may be related with the activation of EGFR, ERK1/2 and PI3K/Akt signaling pathways.

目的 探讨99锝[99Tc]亚甲基二膦酸盐(99Tc-MDP)对胶原诱导性关节炎(CIA)大鼠的治疗作用.方法 设立正常组大鼠10只,建立CIA大鼠模型18只,分为模型组和99Tc-MDP组各9只.99Tc-MDP组CIA大鼠予以尾静脉注射99Te-MDP,相当于99TC 0.04ug·kg-1·d-1共21 d .测量各组大鼠体重、关节肿胀程度和关节炎指数(AI),观察滑膜病理组织形态学变化,并用ELISA法检测血清肿瘤坏死因子(TNFα)水平.结果 ①与正常组大鼠比较,模型组CIA大鼠体重明显减轻.关节肿胀程度严重,AI评分明显升高,滑膜组织病理评分也明显升高(均P＜0.01);②99Tc-MDP干预治疗可明显缓解CIA大鼠体重下降,改善关节肿胀程度,降低AI评分和滑膜组织病理评分;③正常对照组和99Tc-MDP组大鼠血清TNFα水平显著性低于模型组大鼠(均P＜0.01).结论 CIA大鼠关节炎症状明显,99Tc-MDP可明显改善CIA大鼠一般状况,减轻关节炎症状及滑膜组织的病理评分,降低血清TNF-α水平,对CIA有显著治疗效果.

BACKGROUND & OBJECTIVE:Epoxyeicosatrienoic acids (EETs) are generated from arachidomic acid by cytochrome P450(CYP). Previous studies revealed very strong and selective expression of CYP expoxygenase in human cancer tissues, but almost none in adjacent normal tissues. This study was to investigate the promotive effect of EETs on proliferation of tumor cells and the possible mechanisms.METHODS:Four tumor cell lines, Tca-8113, A549, Ncl-H446 and HepG2, were treated with different concentrations of EETs (8,9-EET, 11,12-EET and 14,15-EET) for 12, 24, 48 and 72 h, respectively. Cell proliferation was measured using the MTT assay. The effect of exogenous EETs on cell cycle of Tca-8113 cells was assessed by flow cytometry. Signal transduction inhibitors of PI3K (LY294002), MAPKK (PD98059), MAPK (apigenin) and PKC (H7) were used to block EETs-induced cell proliferation. Expressions of the total protein and phosphorylated ERK1/2 and Akt were determined by Western blot.RESULTS:EETs promoted proliferation of tumor cells compared with the control and vehicle group in a dose-and time-dependent manner (P<0.01). Incubation of tumor cells with EETs markedly increased the cell number at S/G2-M phase. The percentages of Tca-8113 cells at S and G2-M phases were (49.7+/-7.5%) vs. (17.2+/-9.7%) (P<0.01) and (21.0+/-5.3%) vs. (4.9+/-7.3%), respectively(P<0.01) with and without the treatment of 11,12-EET. EETs incubation significantly enhanced phosphorylation of MARK as well as PI3K/Akt in tumor cells. LY294002, PD98059, apigenine and H7 reduced the stimulative effect of EETs on cell proliferation.CONCLUSION:EETs possess the promotive effect on proliferation of tumor cells via activation of MAPK and PI3K/Akt signal pathways.

患者,女性,57岁.因发现血象三少6年,眼干2年,口干2个月,发热1周于2006年11月9日收入院.患者于2000年11月在治疗慢性支气管炎的过程中多次查血常规均示血象三少,作骨髓细胞学检查无异常,使用补血药治疗无明显效果.

成人Still's病(AOSD)是一种少见的不明原因的系统性炎症反应性疾病,以弛张热、一过性皮疹、关节炎和多器官受累为特点.其名字来源于Geoge Still,在1897年一篇专著上描述了22名儿童出现的在目前称为幼年类风湿关节炎的症状和体征.1971年Eric Bywaters报道了14例成人类似儿童Still's病的临床表现,该病名就此开始使用.因为目前该病的发生似有增多,而对其诊断又缺乏特异性的方法,极易引起误诊和漏诊,为提高对本病的认识,现综述如下.

目的探讨氨苯砜(DDS)过敏反应综合征的临床特征和治疗方法。方法报告1例氨苯砜过敏反应综合征并复习相关文献。结果本例患者服用2周DDS后出现发热、皮疹、肝脾肿大、淋巴结肿大、肝损害、异型淋巴细胞增多和低丙种球蛋白血症,确诊为氨苯砜过敏反应综合征,经糖皮质激素治疗效果显著。结论氨苯砜过敏反应综合征的临床特征为发热、皮疹、淋巴结肿大、肝损害和溶血性贫血等。根据DDS的用药史,排除微生物感染和其它相关疾病,可诊断本病。治疗上应尽快使用足量的糖皮质激素并逐步减量维持治疗1个月以上。

系统性红斑狼疮(SLE)的特点为多脏器损害,伴有异常的免疫反应.心脏瓣膜病变是SLE严重的并发症.本文报告1例SLE合并心脏瓣膜病变患者的临床资料和治疗情况,并复习有关文献.