目的   采用两样本孟德尔随机化以及Meta分析研究趋化因子C-X3-C基序配体1（CX3CL1）表达水平与系统性红斑狼疮（SLE）发病风险的因果关系。方法   获取CX3CL1表达水平与SLE的全基因组关联研究（GWAS）数据，将单核苷酸多态性（SNP）作为工具变量并选择敏感的SNPs进行分析。通过逆方差加权法（IVW）、加权中位数法（WM）、MR-Egger回归法进行两样本MR分析，以OR值评估CX3CL1表达水平与SLE之间的因果关系，并对结果进行异质性和多效性检验。最后利用R软件Meta包进行Meta分析。利用coloc包进行共定位分析。结果   纳入9个SLE作为结局变量，其中4个变量ebi-a-GCST90018917（OR=2.14，95%CI：1.50~3.06），ebi-a-GCST003156（OR=2.25，95%CI：1.00~5.06），ebi-a-GCST90014238（OR=3.02，95%CI：1.54~5.94），finn-b-SLE_NOS（OR=1.81，95%CI：1.01~3.22）表明CX3CL1表达水平与SLE之间存在因果关系。关于 OR 95% CI 的森林图显示 SLE 患者的CX3CL1表达水平显著高于健康人群（OR=1.87，95%CI：1.53~2.29，P＜0.001）。共定位分析结果提示CX3CL1表达水平和SLE表型之间有共享的遗传变异位点（rs170364）。结论  CX3CL1表达水平与SLE存在正向因果关系，CX3CL1表达水平的升高使得SLE的发病风险升高。

       Objective  To investigate the causal  relationship  between CX3CL1 levels and the  risk of  systemic lupus erythematosus（SLE）using two-sample Mendelian randomization and Meta-analysis methods．Methods  Genome-Wide Association Study（GWAS）data for CX3CL1 levels and SLE were obtained．Single nucleotide polymorphisms（SNPs）were used as instrumental variables，and sensitive SNPs were selected for analysis．Two-sample Mendelian  randomization was performed using the inverse variance weighted（IVW）method，weighted median（WM）method，and MR-Egger  regression to evaluate the causal relationship between CX3CL1 levels and SLE，with OR values assessing this relationship．Heterogeneity and pleiotropy tests were conducted on the results．Meta-analysis was performed using the Meta package in R software，and colocalization analysis was conducted using the coloc package．Results  Nine SLE outcomes were included as outcome variables，with four variables（ebi-a-GCST90018917［OR=2.14，95%CI：1.50-3.06］，ebi-a-GCST003156［OR=2.25，95%CI：1.00-5.06］，ebi-a-GCST90014238［OR=3.02，95%CI：1.54-5.94］，finn-b-SLE_NOS［OR=1.81，95%CI：1.01-3.22］）indicating a causal relationship between CX3CL1 expression levels and SLE．The forest plot for OR 95%CI showed that CX3CL1 expression levels in SLE patients were significantly higher than in healthy individuals（OR=1.87［95%CI：1.53-2.29］，P＜0.001）．Colocalization analysis suggested that there was shared genetic variation sites（rs170364）between CX3CL1 expression levels and SLE phenotype．Conclusions  There is a positive causal relationship between CX3CL1 expression levels and SLE，with increased CX3CL1 levels elevating the risk of developing SLE．

目的 运用三维斑点追踪成像(3D-STE)技术,检测系统性红斑狼疮(SLE)患者的左室收缩期峰值应变(S)和应变率(Sr)及舒张指数,探讨其评价 SLE 患者左室整体收缩及舒张功能的临床应用价值。方法 选择 30 例 SLE 患者(SLE 组)和 30 例正常人(对照组),分别对其进行二维超声心动图和3D-STI检查,获取心尖四腔、两腔、三腔及心尖长轴二维超声及M型超声切面,测量左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVEDs)、室间隔舒张末期厚度(IVSd)、室间隔收缩末期厚度(IVSs)、左心室后壁舒张末期厚度(LVPWd)、左心室后壁收缩末期厚度(LVPWs)、左心室射血分数(LVEF)、左心室缩短分数(LVFS)、每搏输出量(SV)、左室舒张末期容积(EDV)、收缩末期容积(ESV)、心输出量(CO)、球形指数(SPI)、左室舒张末期质量(LV EDmass)、左室收缩末期质量(LV ESmass)。应用3D-STI行心肌运动分析, 测量左心室整体纵向、圆周、径向及面积收缩期峰值应变(GLS、GCS、GRS、GAS),经胸采集四维全容积图像,应用公式计算各方向相应的舒张期前1/3点时的应变显像舒张指数(SI-DI),公式为(SI-DI=(A-B)/A×100%)。应用统计学分析上述指标在各组间的差异性及其之间的相关性。结果 SLE 组超声心动图的测量数值(LVEF、 LVFS、SV、EDV、CO、LV EDmass、LV ESmass)较对照组降低,差异有统计学意义(P＜0.05),(LVEDd、LVEDs、IVSd、IVSs、LVPWd、LVPWs、ESV、SPI) 与对照组比较, 差异亦均无统计学意义(P＞0.05)。SLE组左心室 GLS、GCS、GRS、GAS均较对照组减低, 差异均有统计学意义(P<0.05)。GAS诊断SLE的敏感度为93.3%,高于GLS(80%)、GCS(66.7%)、GRS(86.7%),GCS诊断SLE的特异度为(93.3%),高于GLS(86.7%)、GAS(86.7%)和GRS(73.3%);应用公式计算得出,SLE组左心室L-SI-DI、C-SI-DI、R-SI-DI 及A-SI-DI均低于正常对照组,差异均有统计学意义(P<0.05);ROC 曲线显示C-SI-DI敏感度(93.3%)及L-SI-DI敏感度(86.7%)高于R-SI-DI(80.0%)、A-SI-DI(80.0%);A-SI-DI特异度(93.3%)及R-SI-DI特异度(93.3%)高于L-SI-DI(73.3%)、C-SI-DI(73.3%)。结论 SLE 患者左室总体收缩及舒张功能减低,4D-STI超声斑点追踪技术可早期检测 SLE 患者左心室收缩及舒张功能的异常。

Objective To detect left ventricular systolic peak strain(S), strain rate(Sr) and diastolic index in patients with systemic lupus erythematosus(SLE) by three-dimensional speckle tracking imaging(3D-STE), and to evaluate the left ventricular total in SLE patients and clinical application value of systolic and diastolic function. Methods Thirty patients with SLE(SLE group) and 30 normal controls(control group) were enrolled. Two-dimensional echocardiography and 4D-STI were performed to obtain sections of apical four-chamber, two-chamber, three-chamber and apical long axis of ultrasound and m-mode ultrasound. To measure left ventricular end-diastolic diameter(LVEDd), left ventricular end-systolic diameter(LVEDs), ventricular septal end-diastolic thickness(IVSd), ventricular septal end-systolic thickness(IVSs), left ventricular posterior wall diastolic end-stage thickness(LVPWd), left ventricular posterior wall end-systolic thickness(LVPWs), left ventricular ejection fraction(LVEF), left ventricular shortening fraction(LVFS), stroke volume(SV), left ventricular end-diastolic volume(EDV), end-systolic volume(ESV), cardiac output(CO), spherical index(SPI), left ventricular end-diastolic mass(LV EDmass), left ventricular end-systolic mass(LV ESmass). 4D-STI myocardial motion analysis, the total longitudinal, circumferential, and radial and area systolic peak strains(GLS, GCS, GRS, GAS) of the left ventricle were measured, and the four-dimensional full-volume images were collected through the thoracic, and the formula was used to calculate the first 1/3 of the diastolic phase in each direction. The formula of strain imaging diastolic index(SI-DI) is(SI-DI=(AB)/A×100%). Statistical analysis was used to analyze the differences between the above indicators and the correlation between the groups. Results The measured values of two-dimensional echocardiography(LVEF, LVFS, SV, EDV, CO, LV EDmass, LV ESmass) in the SLE group were lower than those in the control group, and the difference was statistically significant(P＜0.05). In LVEDd, LVEDs, IVSd, IVSs, LVPWd, LVPWs, SPI, there were no significant differences compared with that of control group(P＞0.05). The left ventricular GLS, GCS, GRS, and GAS in the SLE group were lower than those in the control group. The differences were statistically significant(P<0.05). The sensitivity of GAS in the diagnosis of SLE was 93.3%, higher than GLS(80%), GCS(66.7%), and GRS(86.7%). The specificity of GCS for the diagnosis of SLE was(93.3%), higher than GLS(86.7%), GAS(86.7%) and GRS(73.3%). The left ventricle L-SI-DI, C-SI-DI, in the SLE group was calculated by the formula. R-SI-DI and A-SI-DI were lower than the normal control group, the difference was statistically significant(P<0.05);the ROC curve showed C-SI-DI sensitivity(93.3%) and L-SI-DI sensitivity(86.7%) was higher than R-SI-DI(80.0%), A-SI-DI(80.0%);A-SI-DI specificity(93.3%) and R-SI-DI specificity(93.3%) was higher than L-SI-DI(73.3%) and C-SI-DI(73.3%). Conclusion Total left ventricular systolic and diastolic function in patients with SLE are reduced. 4D-STI ultrasound speckle tracking technique can detect left ventricular systolic and diastolic dysfunction in patients with SLE.

目的 探讨黏附因子E-钙粘蛋白(E-cadherin)和Toll样受体9(TLR9)在系统性红斑狼疮(SLE)发病机制中的作用。方法 随机选取SLE患者41例,健康对照组18例,采用酶联免疫吸附试验(ELISA)法检测血清中sE-cadherin的表达,采用流式细胞技术(FCM)检测外周血单核细胞上TLR9的表达。分析 sE-cadherin,TLR9与系统性红斑狼疮患者病情的活动性。结果 SLE组血清中sE-cadherin的表达水平高于正常组(P=0.00),差异有统计学意义;SLE活动组血清中sE-cadherin表达水平高于稳定组(P=0.06),但差异无统计学意义;SLE组TLR9表达高于健康组(P=0.00),活动组高于稳定期组(P=0.00),差异均有统计学意义;SLE患者TLR9表达与SLEDI呈正相关(r=0.727,P=0.00),差异有统计学意义。结论 血清中sE-cadherin和外周血单核细胞内TLR9均参与了SLE患者病情发展的过程,并且二者在SLE发病机制中可能具有协调作用。

Objective To explore the effect of adhesion molecule E-cadherin and Toll-like receptor-9(TLR9) in the pathogenesis of systemic lupus erythematosus(SLE). Methods 41 patients with SLE and 18 healthy controls were selected randomly.Expression of TLR9 in peripheral blood mononuclear cells determined by FCM. SE-cadherin levels were measured in the serum by ELISA analysis. The correlation between sE-cadherin、TLR9 and the patient's condition of SLE was analyzed. Results Compared with healthy subjects,the expression of sE-cadherin in serum was higher among SLE patients(P=0.00),there was statistically significant between two groups;activity group was higher than inactivity group and healthy controls(P=0.06),but there was no statistically significant between activity group and inactivity group. Compared with healthy subjects,the expression of TLR9 in peripherql blood mononuclear cells was higher among SLE patients(P=0.00);activity group was higher than inactivity group(P=0.00),there was all statistically significant between two groups.The positive correlation was observed between TLR9 expression levels and clinical measure of the SLEDAI(r=0.727,P=0.00),there was statistically significant between two groups. Conclusion SE-cadherin and TLR9 may play an important role in SLE,and may interact with each other which needed further study.

目的 观察甲氨蝶呤(MTX)联合激素、羟氯喹治疗轻、中度活动性系统性红斑狼疮(SLE)的实验室结果分析及临床应用价值。方法 选择我院收治的系统性红斑狼疮患者60例,随机分成研究组(n=30)与对照组(n=30),对照组给予糖皮质激素0.5～1.0 mg/(kg·d)及羟氯喹治疗,研究组给予口服MTX片剂每周一次7.5～15 mg联合糖皮质激素及羟氯喹(用法同对照组),比较分析两组患者的实验室检查结果差异。结果 与治疗前相比,研究组患者的ANA、抗ds-DNA滴度及ESR、CRP的下降都明显优于对照组(P＜0.05);研究组患者的ALT、AST、BUN、SCr及血象(WBC、Hb、PLT)指标也明显优于对照组(P＜0.05);研究组患者补体(C3、C4) 也明显高于对照组(P＜0.05)。结论 加用MTX治疗SLE有效,安全性良好,且联合治疗能更好地控制疾病,减少复发,防止及延缓重要脏器的损害。缓解患者的临床症状,为SLE患者提供一个安全、有效的治疗方案。

目的 探讨系统性红斑狼疮(SLE)患者外周血中25-羟基维生素D(25-OH-D)和白介素-17(IL-17)水平的变化及其临床意义。方法 选取40例SLE患者作为研究对象, 20例健康体检人员为健康对照组。运用电化学发光法检测25-OH-D水平,酶联免疫吸附法检测IL-17水平。结果 SLE患者25-OH-D水平明显低于健康对照组(P<0.01),活动期SLE患者25-OH-D水平明显低于缓解期患者(P<0.01)。SLE患者IL-17水平明显升高(P<0.01)。低25-OH-D水平与肾损害(P<0.01)相关,与疾病活动度评分(SLEDAI评分)(r=-0.844,P<0.01)及IL-17水平(r=-0.596,P<0.01)负相关。结论 SLE患者25-OH-D水平降低,低25-OH-D水平与肾损害、病情活动及高IL-17水平相关,25-OH-D可能参与了SLE的炎症进程。

Objective To assess the 25-hydroxyvitamin D (25-OH-D) and interleukin-17(IL-17) status in patients with systemic lupus erythematosus(SLE) and its clinical significance. Methods 40 SLE patients along with 20 matched controls were collected. Chemilumineseent immunoassay (CLIA) was used to detect the levers of serum 25-OH-D. The levels of serum IL-17 were evaluated using enzyme-linked immunosorbent assay (ELISA). Results Serum 25-OH-D level in SLE patients was significantly lower than in healthy controls (P<0.01). Serum 25-OH-D level in active SLE patients was significantly lower than in inactive SLE patients (P<0.01). Lever of IL-17 was significantly higher in SLE patients than in healthy controls (P<0.01). Insufficiency of 25-OH-D was related to renal disorders. Serum 25-OH-D level was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI) scores(r=-0.844, P<0.01)and serum levels of IL-17(r=-0.596, P<0.01). Conclusion Insufficiency of 25-OH-D is prevalent in SLE patients. It is associated with nephritis, disease activity and high serum levels of IL-17, thus it may play an important part in the inflammatory process in SLE.

目的 探讨系统性红斑狼疮(SLE)患者并发感染的影响因素并提出相应对策。方法 统计2012年1月—2015年12月在风湿免疫科住院的SLE患者,依据是否存在感染分为两组:感染组和非感染组。查电子病历记录感染组患者感染部位、所感染病原体的种类、免疫抑制治疗方案、病程、住院次数、血液生化指标、红细胞沉降率、肝肾功能以及补体C3、C4 水平,分析SLE患者发生感染的危险因素。结果 近三年风湿免疫内科共收治SLE患者302例,合并感染44例,发生感染63例次,感染发生率7.32%,高于全院感染发生率2.82%,差异有统计学意义(P<0.05)。呼吸系统感染有43例次,占68.25%,是患者最常见的感染部位。单因素分析显示,激素的冲击治疗、血红蛋白降低、白蛋白降低和血清肌酐水平异常(P<0.01)及ESR异常(P<0.05)是医院感染的危险因素。结论 SLE患者感染发生率高,免疫抑制剂冲击治疗、有合并症患者更易发生感染。应合理使用免疫抑制剂,密切留意患者感染症状,并定期检测血红蛋白、白蛋白及ESR等各项实验室指标,及时发现感染并进行病原学培养,做到尽早、合理治疗。