原发性干燥综合征合并间质性肺病的临床特征

目的探讨原发性干燥综合征（primary Sjogen’s syndrome,pSS）合并间质性肺病（interstitial lung disease．ILD）的临床及影像学特点,以提高对原发性干燥综合征合并间质性肺病（pSS—ILD）的认识。方法回顾性分析本院2004年1月．2007年12月确诊且资料完整的219例pSS患者,对其中47例合并ILD患者的临床特点及影像学检查进行分析。结果（1）pSS组ILD的发生率为21．46％,pSS-ILD组发病年龄晚于pSS一无ILD组,且病程长于pSS．无ILD组（P〈O．01）;（2）pSS-ILD组血沉（erythroeyte sedimentation rate,ESR）明显增快,C反应蛋白（C-reaetive protein,CRP）明显增高,两者与pSS-无ILD组比较差异均具有统计学意义（P〈0．01）;（3）pSS-ILD组抗SSA抗体阳性率高于pSS-无ILD组（P〈0．05）;抗核抗体（antinuclear antibody,ANA）、类风湿因子（rheumatoid factor。RF）、抗SSB抗体、血浆球蛋白〉30g／L、低补体C3和低补体C4在两组间无明显差异;（4）在诊断pSS—ILD病变时,肺高分辨率CT（high resolution computerized tomography,HRCT）明显优于普通X线胸片。结论ILD是pSS常见的系统损害。pSS-ILD的发生与疾病的活动及某些自身抗体有关,肺HRCT有助于pSS—ILD患者的早期诊断及预后判断。     

系统性红斑狼疮患者T淋巴细胞PTA1表达的研究

目的：研究血小板和T细胞活化抗原1（PTA1）在系统性红斑狼疮（SLE）外周血T淋巴细胞的表达及其与SLE活动相关性，探索活化T细胞在SLE发病中的作用。方法：应用双色直接荧光标记，流式细胞仪分析27例（其中活动期13例，非活动期14例）SLE患者和30名健康志愿者的CD3，CD4，CD8淋巴细胞，在植物血凝素（PHA）刺激下PTA1（CD226）表达，同时检测SLE患者抗dsDNA抗体，C3和C4补体，疾病活动度用SLEDAI记分，结果：SLE患者组CD3，CD4，CD8淋巴细胞上PTA1表达率均高于正常对照组，CD3上PTA1表达两组差异有显著性（P＜0．01），活动期SLE组CD3，CD4，CD8细胞上PTA1表达均高于正常对照组和非活动期SLE组（P＜0．01），而非活动期SLE组与正常对照组差异无显著性（P＞0．05），SLE患者CD3，CD8细胞PTA1表达与SLEDAI，抗dsDNA抗体之间呈正相关，与C3，C4补体水平呈负相关，CD8细胞PTA1表达与SLEDAI，抗dsDNA抗体，C3，C4补体水平呈直线相关（P＜0．05），结论：SLE患者存在T细胞亚群异常活化，活动期SLE淋巴细胞PTA1表达增高，SLE患者CD8细胞PTA1表达异常与SLEDAI，抗dsDNA抗体，C2和C4补体之间有明显相关，CD8细胞活化程度与SLE疾病程度有关，PTA1可能参与了SLE的免疫发病机制。     

SLE活动期血清白蛋白、球蛋白比例变化的临床意义

检测28例系统性红斑狼疮（SLE）患者治疗前后的血清白蛋白（A）、球蛋白（G）、抗dsDNA、补体C3，观察上述指标在病情活动期与非活动期的差异及A／G比例与SLE疾病活动指数（SLEDAI）、抗dsDNA和补体C3的相关性；并与正常对照组比较。结果SLE活动期与非活动期、对照组比较，血清A、G、A／G比例、抗dsDNA、补体C3均有显著统计学差异（P〈0．01）；病程中A／G比例与SLEDAI、抗dsDNA和补体C3均相关，认为SLE活动期血清A／G比例显著性降低，能反映SLE病情变化。     

65例系统性红斑狼疮患者抗中性粒细胞胞浆抗体的检测分析

目的探讨抗中性粒细胞胞浆抗体(ANCA)与系统性红斑狼疮(SLE)的关系及临床意义.方法回顾性分析65例SLE患者的ANCA检测结果; ANCA与SLE主要临床表现、实验室检查结果的关系; SLE患者病情活动组与非活动组ANCA阳性率的比较.结果 IIF法检测ANCA在SLE中的阳性率是61.5 %,ANCA阳性组中有血管炎皮损(67.5 %)及浆膜炎(55.0 %)者明显高于阴性组(P<0.05);同时ANCA阳性组与阴性组比较,在24 h尿蛋白大于0.5 g/L,血红蛋白低于90 g/L,抗ds-DNA抗体阳性,低补体血症方面差别有统计学意义(P<0.05).结论提示ANCA可能是判断SLE病情复发与缓解的一个有用指标,推测ANCA与活动性狼疮肾炎有关.     

抗中性粒细胞胞质抗体与系统性红斑狼疮的相关性研究

目的探讨抗中性粒细胞胞质抗体（ANCA）与系统性红斑狼疮（SLE）的相关性及其临床意义。方法收集活动组和非活动组各50例SLE患者的临床和实验室资料,间接免疫荧光（IIF）方法检测患者血清ANCA,AN-CA阳性者加做髓过氧物酶（MPO）、蛋白酶3（PR3）的酶联免疫检测（ELISA）。结果①活动组SLE患者ANCA阳性率（64.0%）高于非活动组（20.0%）及对照组（2.0%）（P均〈0.05）;②ANCA阳性组与阴性组比较,在临床表现（胸膜炎、心包炎、肾损害方面）2、4 h尿蛋白〉0.5 g/d、抗ds-DNA抗体阳性、低补体血症方面差异有统计学意义（P〈0.05）;③ANCA阳性的狼疮肾炎组MPO-ANCA阳性率（71.4%）高于非狼疮肾炎组（25.0%）,P=0.038。结论 ANCA与SLE发病和疾病活动有关,可能是判断SLE病情复发与缓解的一个有用指标;MPO-ANCA可能和狼疮肾炎存在密切相关性。     

系统性红斑狼疮细胞与其病情活动性的相关性研究

目的 观察系统性红斑狼疮（SLE）患者外周血狼疮细胞（LEC）形态的变化，探讨其与SLE疾病活动性的关系。方法 采用经典改良血块法观察了50例SLE疾病活动期和30例SLE非活动期患者外周血LEC形态，同时与血清自身抗体、补体及SLE疾病活动指数（SLEDAI）对比研究。结果 特殊形态的LEC与自身抗体的抗dsDNA抗体和抗核小体抗体（AnuA）（r=0．588，P=0．056；r=0．759，P=0．135），补体C3和C4（r=-0．648，P=0．058；r=-0．589，P=0．057）及SLEDAI（r=0．686．P〈0．05）具有明显相关性。SLE活动期组特殊型LEC、自身抗体和补体与SLE非活动期组差异有统计学意义（P〈0．01）。当自身抗体和补体与SLEDAI无相关性时，特殊型LEC仍具有良好的相关性（r=0．786，P〈0．05）。结论 特殊型LEC与自身抗体、补体及SLEDAI有明显的相关性，可作为判断SLE疾病活动性的独特指标。     

血清C1q抗体水平与系统性红斑狼疮活动性和狼疮肾炎的关系

目的分析探讨血清C1q抗体水平与系统性红斑狼疮（SLE）活动性以及狼疮肾炎之间的关系。方法采用ELISA方法检测92例SLE患者C1q抗体水平。并与其他SLE活动性指标进行相关分析。结果SLE患者C1q抗体阳性率为67.4%。活动性狼疮组的C1q抗体阳性率及C1q抗体水平显著高于非活动性狼疮组（P〈0.001）。活动性狼疮肾炎组C1q抗体阳性率（P〈0.05）和C1q抗体水平（P〈0.01）显著高于非活动性狼疮肾炎组。联合抗dsDNA抗体检测,没有1例活动性狼疮肾炎患者的C1q抗体和抗dsDNA抗体同时阴性。结论血清C1q抗体与狼疮活动以及活动性狼疮肾炎关系密切,C1q抗体的检测有助于活动性狼疮的诊断,联合抗dsDNA抗体的检测是活动性狼疮肾炎的特异性检测指标。     

抗细胞膜DNA自身抗体快速检测系统性红斑狼疮

目的 探讨抗细胞膜DNA自身抗体（mDNA)在系统性红斑狼疮患者的表达以及这种特异抗体与抗dsDNA抗体的不同。方法 用间接免疫荧光法观察培养的HL60细胞的特异性细胞膜的荧光图形。结果 抗细胞膜DNA自身抗体在SLE患者90例中有81例阳性（阳性率90％）,而在类风湿关节炎（RA）患者35例,强直性脊柱炎（AS）患者31例和健康献血员42名中均为阴性,在干燥综合征（SS）患者20例中有1例阳性（阳性率5％）,抗细胞膜DNA自身抗体对SLE诊断的特异性为98．8％。结论 抗细胞膜DNA自身抗体是一种诊断。SLE的新的标记抗体,其敏感性高（90．0％）,特异性强（98．8％）,较抗dsDNA抗体、抗Sm抗体检测更先进。     

抗核小体抗体、抗双链DNA抗体和抗超敏双链DNA抗体与系统性红斑狼疮的相关性研究

目的 通过检测系统性红斑狼疮(SLE)患者血清中抗核小体抗体(AnuA)、抗双链DNA (dsDNA)抗体和抗超敏双链DNA (dsDNA-NcX)抗体的水平,分析其在SLE患者中的敏感性、特异性及与其他实验室指标的相关性.方法 采用酶联免疫吸附试验(ELISA)法分别检测91例SLE患者、45例非SLE疾病对照和46例健康对照组血清中AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的水平,比较3种抗体对SLE诊断的敏感性和特异性,评价其与其他实验室指标的关系.结果 SLE患者AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的阳性率分别为49.45％、56.04％和61.54％;特异性分别为94.51％、94.51％和100.00％.AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体均与SLEDAI评分呈正相关(r=0.50,P=0.00;r =0.49,P=0.00;r =0.42,P=0.00).ANA的滴度与AnuA的浓度呈正相关(r=0.30,P=0.00),与抗dsDNA抗体的滴度无相关性(r=0.19,P=0.08),与抗dsDNA-NcX抗体的浓度呈正相关(r=0.50,P=0.00).红细胞沉降率在抗dsDNA-NcX抗体、抗dsDNA抗体阴性和阳性组间比较差异无统计学意义(x2=0.76,P=0.38;x2=0.13,P=0.18),而在AnuA阴性与阳性组间比较差异有统计学意义(x2 =20.31,P=0.00).CRP及24小时尿蛋白定量在三者阴性与阳性组间比较差异无统计学意义.补体C3、C4在AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的阴性与阳性组间比较差异有统计学意义(x2=9.84,P=0.00;x2=16.53,P=0.00;x2 =10.33,P=0.00;x2 =11.61,P=0.00;x2 =12.69,P=0.00;x2=8.77,P=0.00).胱抑素在抗dsDNA抗体和AnuA的阴性与阳性组间比较差异无统计学意义,而在抗dsDNA-NcX抗体阴性与阳性组间比较差异有统计学意义(x2 =4.04,P=0.04).结论 抗dsDNA-NcX抗体可作为SLE的特异性抗体之一,其敏感性和特异性均高于抗dsDNA抗体和AnuA,三者均与SLE的疾病活动相关,联合检测有助于评估病情.     

抗核小体抗体与抗C1q抗体在狼疮肾炎血清的表达及其临床意义

目的探讨抗核小体抗体与抗C1q抗体在狼疮肾炎（lupus nephritis，LN）患者血清的表达及其临床意义。方法使用酶联免疫吸附试验（ELISA）对46例LN患者血清进行检测，并与31例无肾炎临床表现的SLE患者作对照。结果LN患者血清中抗核小体抗体与抗C1q抗体浓度及阳性率显著高于SLE对照组（P〈0．01）。抗双链DNA（dsDNA）抗体、抗Sm抗体、抗nRNP抗体、抗心磷脂（aCL）IgG抗体有较高的阳性率，与对照组相比差异有统计学意义（P〈0．05）。将抗核小体抗体、抗C1q抗体、抗dsDNA抗体、抗Sm抗体、抗nRNP抗体和aCLIgG抗体分别引入Logistic回归进行统计分析，结果显示入选的自变量包括抗核小体抗体、抗C1q抗体、抗dsDNA抗体（P〈0．05）。结论在LN患者中，存在着抗核小体抗体、抗C1q抗体的高表达。抗核小体抗体及抗C1q抗体在LN发病中起重要的作用。抗核小体抗体、抗C1q抗体、抗dsDNA抗体是反映SLE患者并发肾脏损害的重要指标，在LN诊断和判定其活动性方面有重要作用。     

Managing a variable disease

Asthma varies in severity over time; consequently, treatment regimens must be sufficiently flexible to be adjusted when necessary. At present, inhaled corticosteroids (ICS) remain the cornerstone of asthma therapy and optimal treatment strategies must consider total daily dose and dosing frequency. The dose responsiveness to ICS varies for different indices of asthma. Symptoms and lung function respond readily to low-dose ICS and the dose-response curve is relatively flat. In contrast, the prevention of asthma exacerbations displays a more pronounced dose-response relationship. In mild asthma, once-daily dosing with budesonide is as effective as twice-daily dosing. However, in moderate-to-severe asthma, four-times daily dosing is better than twice-daily dosing for obtaining maximal benefit with minimal side effects. A flexible treatment regimen, consisting of low-dose maintenance treatment combined with high dose and frequently dosed ICS at the earliest sign of an exacerbation, has been shown to be effective. This could be achieved using a single inhaler combination product if the beta(2)-agonist moiety allows for the same flexibility in dosing. Formoterol, with its wide dose range, rapid onset and long duration of effect, has the pharmacological features that permit this versatile, flexible dosing. As a result, Symbicort would seem to offer the flexibility required in a single inhaler for maintenance and reliever purposes in the management of this variable disease.     

Inflammatory bowel disease and thromboembolism

Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown, but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature, as well as in the systemic circulation. Clinicians’ awareness of the risks, and their ability to promptly diagnose and manage tromboembolic complications are of vital importance. In this review we discuss how thromboembolic disease is related to IBD, specifically focusing on: (1) the epidemiology and clinical features of thromboembolic complications in IBD; (2) the pathophysiology of thrombosis in IBD; and (3) strategies for the prevention and management of thromboembolic complications in IBD patients.     

Liver disease and Helicobacter

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Inflammatory bowel disease:Pathogenesis

Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,is characterized by chronic relapsing intestinal inflammation.It has been a worldwide health-care problem with a continually increasing incidence.It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut,catalyzed by the genetic susceptibility of the individual.Although the etiology of IBD remains largely unknown,it involves a complex interaction between the genetic,environmental or microbial factors and the immune responses.Of the four components of IBD pathogenesis,most rapid progress has been made in the genetic study of gut inflammation.The latest internationally collaborative studies have ascertained 163susceptibility gene loci for IBD.The genes implicated in childhood-onset and adult-onset IBD overlap,suggesting similar genetic predispositions.However,the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD.Meanwhile,the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD,as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation.Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms,including the innate and adaptive immunity,and the interactions between genetic factors and microbial and environmental cues.In this review,we provide an update on the major advances that have occurred in above areas.     

Immunopathology of inflammatory bowel disease

Inflammatory bowel disease(IBD)results from a complex series of interactions between susceptibility genes,the environment,and the immune system.The host microbiome,as well as viruses and fungi,play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system.New technologies have allowed researchers to be able to quantify the various components of the microbiome,which will allow for future developments in the etiology of IBD.Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells,innate lymphoid cells,cells of the innate(macrophages/monocytes,neutrophils,and dendritic cells)and adaptive(T-cells and B-cells)immune system,and their secreted mediators(cytokines and chemokines).Either a mucosal susceptibility or defect in sampling of gut luminal antigen,possibly through the process of autophagy,leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity.The antigen presenting cells then mediate the differentiation of na?ve T-cells into effector T helper(Th)cells,including Th1,Th2,and Th17,which alter gut homeostasis and lead to IBD.In this review,the effects of these components in the immunopathogenesis of IBD will be discussed.     

Diagnosis of human prion disease

With the discovery of the prion protein (PrP), immunodiagnostic procedures were applied to diagnose Creutzfeldt-Jakob disease (CJD). Before development of the conformation-dependent immunoassay (CDI), all immunoassays for the disease-causing PrP isoform (PrPSc) used limited proteolysis to digest the precursor cellular PrP (PrPC). Because the CDI is the only immunoassay that measures both the protease-resistant and protease-sensitive forms of PrPSc, we used the CDI to diagnose human prion disease. The CDI gave a positive signal for PrPSc in all 10-24 brain regions (100%) examined from 28 CJD patients. A subset of 18 brain regions from 8 patients with sporadic CJD (sCJD) was examined by histology, immunohistochemistry (IHC), and the CDI. Three of the 18 regions (17%) were consistently positive by histology and 4 of 18 (22%) by IHC for the 8 sCJD patients. In contrast, the CDI was positive in all 18 regions (100%) for all 8 sCJD patients. In both gray and white matter, approximately 90% of the total PrPSc was protease-sensitive and, thus, would have been degraded by procedures using proteases to eliminate PrPC. Our findings argue that the CDI should be used to establish or rule out the diagnosis of prion disease when a small number of samples is available as is the case with brain biopsy. Moreover, IHC should not be used as the standard against which all other immunodiagnostic techniques are compared because an immunoassay, such as the CDI, is substantially more sensitive.     

Enterolithiasis-associated ileus in Crohn's disease

Stasis of the flow of the intestinal contents, ingested material and unfavorable composition of the chylus can lead to the formation of enteroliths inside the bowel. Enterolithiasis represents a rare disorder of the gastrointestinal tract that can be associated with intermittent abdominal pain or more serious complications such as bleeding or obstruction. Enterolithiasis in Crohn’s disease represents an extremely rare condition and usually occurs only in patients with a long symptomatic history of Crohn’s disease. We report an unusual case of enterolithiasis-related intestinal obstruction in a young male patient with Crohn’s disease (A2L3B1 Montreal Classification for Crohn’s disease 2005) undergoing emergency laparotomy and ileocoecal resection. In addition, we present an overview of the relevant characteristics of enterolithiasis on the basis of the corresponding literature.     

Disease monitoring in inflammatory bowel disease

The optimal method for monitoring quiescent disease in patients with Crohn's disease(CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive,costly,and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease(IBD),but the most widely adopted biomarkers are C-reactive protein(CRP) and fecal calprotectin(FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing,traditionally used for colorectal cancer screening,is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers,clinical status,and endoscopic evaluation,the best treatment decisions can be made for the patient with IBD.     

Thiopurines in inflammatory bowel disease revisited

Although a great variety of new drugs have been introduced for the therapy of inflammatory bowel diseases so far,a definite cure of the disease is still out of scope.An anti-inflammatory approach to induce remission followed by maintenance therapy with immunosupressants is still the mainstay of therapy.Thiopurines comprising azathioprine and its active metabolite mercaptopurine as well as tioguanine,are widely used in the therapy of chronic active inflammatory bowel disease(IBD).Their steroid sparing potential and efficacy in remission maintenance are out of doubt.Unfortunately,untoward adverse events are frequently observed and may preclude further administration or be life threatening.This review will focus on new aspects of thiopurine therapy in IBD,its efficacy and safety.     

Correlations between endoscopic and clinical disease activity indices in intestinal Behcet's disease

AIM:To develop a novel endoscopic severity model of intestinal Behcet's disease(BD) and to evaluate its feasibility by comparing it with the actual disease activity index for intestinal Behcet's disease(DAIBD).METHODS:We reviewed the medical records of 167 intestinal BD patients between March 1986 and April 2011.We also investigated the endoscopic parameters including ulcer locations,distribution,number,depth,shape,size and margin to identify independent factors associated with DAIBD.An endoscopic severity model was developed using significant colonoscopic variables identified by multivariate regression analysis and its correlation with the DAIBD was evaluated.To determine factors related to the discrepancy between endoscopic severity and clinical activity,clinical characteristics and laboratory markers of the patients were analyzed.RESULTS:A multivariate regression analysis revealed that the number of intestinal ulcers(≥ 2,P = 0.031) and volcanoshaped ulcers(P = 0.001) were predictive factors for the DAIBD.An endoscopic severity model(Y) was developed based on selected endoscopic variables as follows:Y = 47.44 + 9.04 × non-Ileocecal area + 11.85 ×≥ 2 of intestinal ulcers + 5.03 × shallow ulcers + 12.76 × deep ulcers + 4.47 × geographicshaped ulcers + 26.93 × volcano-shaped ulcers + 8.65 ×≥ 20 mm of intestinal ulcers.However,endoscopic parameters used in the multivariate analysis explained only 18.9% of the DAIBD variance.Patients with severe DAIBD scores but with moderately predicted disease activity by the endoscopic severity model had more symptoms of irritable bowel syndrome(21.4% vs 4.9%,P = 0.026) and a lower rate of corticosteroid use(50.0% vs 75.6%,P = 0.016) than those with severe DAIBD scores and accurately predicted disease by the model.CONCLUSION:Our study showed that the number of intestinal ulcers and volcano-shaped ulcers were predictive factors for severe DAIBD scores.However,the correlation between endoscopic severity and DAIBD(r = 0.434) was weak.