Cutaneous mucosa-associated lymphoid tissue lymphoma complicating Sjögren's syndrome:A case report and review of literature

BACKGROUND The association of Sjögren's syndrome(SS)and lymphoma is similar.Mucosaassociated lymphoid tissue(MALT)or extranodal marginal zone B-cell lymphoma was the most common lymphomatous histology in SS patients.MALT in SS patients is frequently located in the parotid gland,while MALT lymphoma of the skin with SS is an exceedingly rare entity that needs to be recognized.CASE SUMMARY A 60-year-old woman presented with a 3-year history of progressive dry mouth associated with a 1-year history of enlarging cutaneous nodules.Physical examination revealed two hard subcutaneous nodules on her right lower leg.The results of Schirmer’s test were positive,despite the absence of dry eyes.Labial salivary gland biopsy revealed lymphocytic infiltration and chronic inflammation with a focus score of 2.The patient was diagnosed with SS.She underwent resection of one cutaneous nodule,and histopathological analysis identified the nodule as MALT lymphoma.Her dry mouth symptoms improved,and the nodules decreased after 6 mo of treatment with hydroxychloroquine sulfate and chemotherapy(thalidomide,cyclophosphamide,and dexamethasone).CONCLUSION Lymphoma is a severe complication of SS,shown by the reported unique case of cutaneous MALT lymphoma with SS.

麦冬多糖对NOD小鼠颌下腺保护作用研究

目的:观察麦冬多糖对NOD小鼠颌下腺的保护作用。方法:给予NOD小鼠麦冬多糖灌胃,并设置羟氯喹阳性对照组,最后用ELISA法检测相关血清细胞因子,并对小鼠的颌下腺做HE染色,用RT-PCR法检测颌下腺IFN-γ与IL-10mRNA的表达水平。结果:和模型相比,麦冬多糖能降低颌下腺淋巴细胞浸润度,并可修复Th1/Th2细胞因子失衡。结论:麦冬多糖对NOD小鼠颌下腺具有保护作用。

Identification and functional analysis of shared gene signatures between systemic lupus erythematosus and Sjogren's syndrome

Background:Systemic lupus erythematosus(SLE)is an autoimmune disease that can affect multiple systems.Sjogren's syndrome(SS)is an autoimmune disease that may be primary SS(pSS)or occur together with other autoimmune diseases,including SLE.This study aimed to explore the shared gene signatures in SLE and pSS.Methods:Gene expression data sets of SLE(GSE50772 and GSE81622)and pSS(GSE84844 and GSE48378)were obtained and analyzed for differentially expressed genes(DEGs)in peripheral blood mononuclear cells(PBMCs).A protein–protein interaction(PPI)network was constructed.Gene ontology(GO)and KEGG pathway enrichment analysis were carried out for the DEGs.Results:We screened 232 and 110 DEGs from the SLE and pSS data sets,respectively.We found 32 shared DEGs,which were all upregulated in patients compared with controls.Among these 32 DEGs,11 genes showed a more than twofold change in all data sets(IFI27,IFI44L,RSAD2,IFIT1,IFI44,USP18,IFI6,HERC5,EPSTI1,OAS1,and OAS3).PPI analysis showed that 29 genes interacted with each other.GO analysis showed that these 32 shared DEGs were mainly enriched in biological processes associated with the type Ⅰ interferon signaling pathway,defense response to viruses,response to viruses,negative regulation of viral genome replication,and the immune response.Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these 32 DEGs were related to virus infection.Conclusion:This study showed that alterations to biological processes associated with the response to virus infection play critical roles in both SLE and pSS.

丹地琼玉颗粒对干燥综合征小鼠唾液腺的影响

目的:探讨丹地琼玉颗粒对干燥综合征(sj觟grensyndrome,SS)模型鼠的治疗作用。方法:用丹地琼玉颗粒低、中、高3种剂量对SS模型小鼠进行干预,并以生理盐水(NS)作为对照,观察丹地琼玉颗粒对SS模型鼠的唾液流量、CD4+T细胞、CD4+/CD8+及自身抗体的影响。结果:丹地琼玉颗粒能增加小鼠唾液流量,抑制Th细胞在唾液腺表达,促使自身抗体转阴。结论:丹地琼玉颗粒具有治疗SS小鼠的作用,其机制可能为抑制淋巴细胞对唾液腺的浸润。

自拟金菊清润胶囊治疗原发性干燥综合征30例临床观察

目的观察自拟金菊清润胶囊治疗原发性干燥综合征的临床疗效。方法将60例原发性干燥综合征患者,按照随机原则,分为治疗组(中药自拟金菊清润胶囊组)与对照组(硫酸羟氯喹组)各30例予以相应治疗,疗程3个月,观察患者临床疗效、中医证候疗效、唾液流量、泪流量、免疫指标的变化。结果治疗组临床、中医证候疗效总有效率优于对照组(86.2%vs 57.1%,89.6%vs 46.4%,P<0.05,P<0.01);单症状起效时间短于对照组(P<0.01);唾液流率、泪流率改善治疗组优于对照组(3.6 mm/5 min±1.4 mm/5 min vs 2.8 mm/5 min±1.5 mm/5 min,2.9g/5 min±2.4g/5 min vs 1.2 g/5 min±0.3g/5 min,P均<0.05),2组间免疫指标比较差异无统计学意义(P>0.05),均未发现明显不良反应。结论自拟金菊清润胶囊能有效改善原发性干燥综合征患者的临床症状及中医证候,缩短临床起效时间,改善唾液流率及泪流率。

试论干燥综合征以燥毒为本

从干燥综合征的病变特点出发 ,阐述了燥毒是其病因基础和病机关键 ,以及燥毒的产生和实质。强调治疗干燥综合征重在解毒清燥 ,佐以滋阴润燥。

运用针刺疗法治疗眼科疾病体会

以单纯针刺、三棱针放血、穴位注射、针药并用等疗法辨证治疗顽固性、复发性睑板腺炎,麻痹性斜视,sj(o)gren综合征,视网膜色素变性等眼科疾病,疗效确切、方法简便。

活血解毒方对干燥综合征小鼠干扰素-γ、B细胞活化因子及其受体的干预作用研究

目的探索活血解毒方对干燥综合征小鼠干扰素(interferon,IFN)-γ、B细胞活化因子(B cell activating factor belonging to the TNF family,BAFF)及其受体BAFF-R的影响及其机制。方法以C57BL/6j小鼠及NOD/Ltj小鼠为实验动物,分别以蒸馏水、白芍总苷混悬液、活血解毒方汤剂灌胃干预,干预过程中观察小鼠一般状态,于干预60天后测量小鼠唾液流率,并取小鼠颌下腺及血清,测量颌下腺指数及血清中BAFF、BAFF-R、IFN-γ及颌下腺BAFF、BAFF-R水平。结果正常组唾液流率均较其他各组高(P<0.05),实验第40天开始,对照组及治疗组的唾液流率开始较模型组升高(P<0.05),而对照组与治疗组之间差异不明显(P>0.05);第60天对照组与治疗组之间差异明显(P<0.05)。颌下腺指数,正常组较模型组、对照组、治疗组高(P<0.05)。模型组较对照组、治疗组低(P<0.05),对照组与治疗组之间差异不明显(P>0.05)。血清BAFF、BAFF-R、IFN-γ及颌下腺BAFF、BAFF-R水平,正常组均较模型组、对照组、治疗组低(P<0.05),模型组较对照组、治疗组高(P<0.05),其中对照组水平高于治疗组(P<0.05),各组之间比较,差异具有统计学意义(P<0.05)。结论活血解毒方可减轻NOD小鼠颌下腺炎症,增加唾液分泌量,降低血清中BAFF、BAFF-R、IFN-γ及颌下腺BAFF、BAFF-R的水平,从而达到治疗干燥综合征的作用。

干燥综合征与免疫细胞

干燥综合征（Ｓｊｇｒｅｎ’ｓＳｙｎｄｒｏｍｅ，ＳＳ）是一种以外分泌腺淋巴细胞浸润为主要病理变化的慢性自身免疫性疾病。虽然此病很常见但其病因及发病机理仍不十分清楚。笔者复习了大量有关ＳＳ与免疫细胞的文献，概述了人类白细胞抗原（ＨｕｍａｎＬｅｕｋｏｃｙｔｅＡｎｔｉｇｅｎ，ＨＬＡ）、郎格罕细胞（ＬａｎｇｅｒｈａｎｓＣｅｌ，ＬＣ）、Ｔ淋巴细胞亚群之间的关系，以及这些免疫细胞与ＳＳ的关系，对ＳＳ的发病机理有进一步的认识。

自身免疫性坏死性肌病伴干燥综合征1例报告并文献复习

目的:提高对自身免疫性坏死性肌病伴干燥综合征的临床诊断和发病机制的认识。方法:对1例自身免疫性坏死性肌病伴干燥综合征患者的临床资料进行整理和分析,并复习相关文献。结果:自身免疫性坏死性肌病伴干燥综合征较少见,通过肌肉活检、唾液腺或唇腺活检可以增加诊断的准确性,经糖皮质激素、免疫抑制剂、辅酶Q等治疗后病情好转。结论:自身免疫性坏死性肌病伴干燥综合征患者早期起病隐匿,易被误诊、漏诊,临床上应重视早期发现、早期诊断。

Traditional Chinese medicine compound ShengJinRunZaoYangXue granules for treatment of primary Sjogren＇s syndrome： a randomized, double-blind, placebo-controlled clinical trial

Background Traditional Chinese medical treatment of primary Sj（o）gren＇s syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions.This study was a multicenter,randomized,doubleblind,placebo-controlled clinical trial of the efficacy and safety of ShengJinRunZaoYangXue granules for the treatment of primary Sj（o）gren＇s syndrome,including the symptoms of dry mouth and dry eye.Methods We undertook a 6-week,double-blind,randomized trial involving 240 patients with primary Sj（o）gren＇s syndrome at five centers in East China.A computer-generated randomization schedule assigned patients at a 2∶1 ratio to receive either ShengJinRunZaoYangXue granules or placebo once daily.Patients and investigators were blinded to treatment allocation.The primary endpoints were the salivary flow rate,Schirmer test results,and sugar test results.Intention-to-treat and per-protocol analyses were performed.Results All 240 patients were randomly allocated to either the treatment group （n=160,ShengJinRunZaoYangXue granules） or placebo group （n=80） and were included in the intention-to-treat analysis.After program violation and loss to follow-up,a total of 199 patients were included in the per-protocol analysis.At six week,intention-to-treat and per-protocol analyses of the left-eye Schirmer I test results showed an improved difference of 1.36 mm/5 min （95% CI：0.03 to 2.69 mm/5 min） and 1.35 mm/5 min （95% CI：0.04 to 2.73 mm/5 min）,respectively,and those of the right-eye Schirmer I test results showed an improved difference of 1.12 mm/5 min （95% CI：0.02 to 2.22 mm/5 min） and 1.12 mm/5 min （95% CI：-0.02 to 2.27 mm/5 min）,respectively.There was no significant difference between the two groups before treatment.After treatment,the between-group and within-group before-and-after paired comparison results were statistically significant （P 〈0.05）.Intention-to-treat and per-protocol analyses showed an improved salivary flow rate by 0.04 ml/15 min （95% CI：-0.49 to 0.58 ml/15 min） and 0.04 ml/15 min （95% CI：-0.52 to 0.60 ml/15 min）,respectively,but the differences were not significant.Intention-to-treat and per-protocol analyses showed that the sugar test results were improved by 1.77 minutes （95% CI：0.11 to 3.44 minutes） and 1.84 minutes （95% CI：0.12 to 3.55 minutes）,respectively,but the differences were not significant.For the secondary endpoint,intention-to-treat and per-protocol analyses showed significant improvement in the integrated evaluation of treated patients with dry eye and dry mouth after six weeks of treatment.The incidence of adverse events was 15.6% in the treatment group and 10.0% in the placebo group.Most （94%） adverse events were mild to moderate in the two groups,and only two cases of serious adverse events occurred in the treatment group; both were caused by autoimmune liver disease.Conclusions Six-week treatment with ShengJinRunZaoYangXue granules for primary Sj（o）gren＇s syndrome in this large-scale study improved the symptoms of dry mouth,dry eyes,and low tear flow rate with minimal adverse events.

Application of immunosuppressant facilitates the therapy of optic neuritis combined with Sj（o）gren＇s syndrome

Background Optic neuritis （ON） is often the first symptom of multiple sclerosis （MS） and neuromyelitis optica （NMO） while there has been very little research reported on ON combined with Sj（o）gren＇s syndrome （SS）.The aim of this study is to provide different treatments and services for and NMO patients combined with SS.Methods Twenty-seven patients with ON combined SS were divided into two groups：corticosteroid group （C group,methylprednisolone sodium succinate,14 patients） and corticosteroid＋ immunosuppressant group （C＋I group,leflunomide,13 patients）.ON relapse times in 1 year after treatment,number of patients who relapsed to NMO/MS in 1 years,visual acuity and retina nerve fiber layer （RNFL） thickness were measured.Mann Whitney-Wilcoxon test was used to compare continuous variables and Chi-square test or Fisher＇s exact test was to compare proportions.Results ON combined with SS patients had higher incidence rates in middle-aged women who have binocular damage and heavier visual function damage or when there is an easy relapse,and the patients are often hormone dependent.The patients are more likely anti-aquaporin-4 IgG seropositive （70.4％）.They are liable to form a centrocecal scotoma and tubular vision.The times of relapse decreased in patients who used immunosuppressant,and a significant difference was found between immunosuppressant and non-immunosuppressant groups in visual acuity recovery during 6-month followup period （P ＜0.05）; however,the RNFL thickness at the four quadrants was not significantly different.Conclusions The effect of immunosuppressant plus corticosteroid on the early onset of ON combined with SS was to provide ON remedy and to prevent recurrence in clinics.This study provides a significant reference for the prevention and treatment of ON on the basis of immunosuppressant and corticosteroid.

Diagnosis of Liver Involvement in Primary Sj(o)gren Syndrome

Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sj(o)gren syndrome (SS).In the 1990s,a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease,liver function and a complete panel of autoantibodies.Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS.The most recent studies have shown that,after eliminating hepatotoxic drugs and fatty liver disease,the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases.The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important,since the two processes require different therapeutic approaches and have different prognoses.With respect to viral infections,chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area,while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries.After eliminating viral hepatitis,primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS.PBC-related SS patients may have a broad spectrum of abnormalities of the liver,including having no clinical or analytical data suggestive of liver disease.Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I),and nearly 10% of these patients have an AIH-PBC overlap.Finally,IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis,especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present.

在喀麦隆原木上截获模斯乳白蚁

本文叙述了从喀麦隆原木上截获的模斯乳白蚁Ｃｏｐｔｏｔｅｒｍｅｓｓｊｓｔｅｄｔｉｖａｒ．ｍａｄｉｃａＳｉｌｖｅｓｔｒｉ。经测量其头长至颚基１．０６～１．０９ｍｍ（１．０７），头宽０．８３～．０８７ｍｍ（０．８６），颚头指数０．４９～０．５３ｍｍ（０．５２）。

Immune Components of Liver Damage Associated with Connective Tissue Diseases

Autoimmune connective tissue diseases are associated with liver abnormalities and often have overlapping pathological and clinical manifestations.As a result,they can present great clinical challenges and evoke questions about diagnostic criteria for liver diseases.Moreover,discriminating between liver involvement as a manifestation of connective tissue disease and primary liver disease can be challenging since they share a similar immunological mechanism.Most patients with connective tissue diseases exhibit liver test abnormalities that likely result from coexisting,primary liver diseases,such as fatty liver disease,viral hepatitis,primary biliary cirrhosis,autoimmune hepatitis,and drug-related liver toxicity.Liver damage can be progressive,leading to cirrhosis,complications of portal hypertension,and liver-related death,and,therefore,must be accurately identified.In this review,we highlight the challenges facing the diagnosis of liver damage associated with connective tissue disease and identify immune mechanisms involved in liver damage associated with connective tissue diseases.

原发性干燥综合征肺脏受累及其危险因素分析

目的 本研究旨在研究pSS患者的肺脏受累情况,并分析其影像学特点,探讨pSS患者发生肺脏受累的危险因素,为pSS患者肺脏受累的诊断及预后评估提供依据.方法 选取2003-2012年北京大学人民医院住院的1 341例SS患者,其中pSS患者853例,继发性SS（sSS）患者488例,分析患者的临床及影像学资料,以其中105例pSS肺脏受累患者为研究对象纳入病例组,选取同期（2008-2012年）84例不合并脏器受累的pSS患者作为对照组,根据美国胸科协会/欧洲呼吸协会（ATS/ERS）特发性间质性肺炎的分类,由2名经验丰富的放射科医师判断pSS肺脏受累的高分辨率CT（HRCT）异常类型、发生部位及肺叶受损面积评分.利用横断面研究探讨pSS患者肺脏受累患者HRCT的受损面积、分布部位及常见类型,利用病例对照分析及Logistic回归探讨肺脏受累危险因素.结果 SS患者肺脏受累发生率为21.70％（291/1341）,其中19.34％（165/853） pSS和25.82％（126/488）sSS患者出现肺脏累及.高球蛋白血症及RF升高在该人群中明显,但抗SSA抗体、抗SSB抗体阳性率仅分别为52.5％和37.8％.pSS肺脏受累患者的HRCT分析示肺脏受累范围广泛,肺下叶受累比例高且肺叶受损面积大.常见HRCT异常类型为线样影（61例,93.8％）、磨玻璃样（57例,87.7％）、胸膜受累（42例,64.6％）、网格状样（41例63.1％）等.病例对照分析发现年龄≥60岁、C4低于正常、RF和ANA阳性的肺脏受累患者所占比例更高,然而,抗SSA阳性患者所占比例更低,差异均有统计学意义（x2=42.338,P＜0.01;x2=3.681,P=0.05;x2=14.171,P＜0.01;x2=10.507,P＜0.01;x2=4.435,P=0.04）.多元Logistic回归示年龄≥ 60岁（OR=7.73）及RF阳性（OR=4.43）为pSS患者发生肺脏受累的独立危险因素（均P＜0.01）.结论 肺脏受累是pSS患者的常见合并症,肺病变广泛且类型多样,下叶受累比例高且受损面积大.高龄及RF阳性为pSS肺脏受累的独立危险因素.

结节病并存原发性干燥综合征四例并文献复习

回顾性分析4例结节病并存原发性干燥综合征（pSS）的临床特点并复习相关文献.4例患者均为女性,均以呼吸道症状就诊,抗核抗体阳性2例,抗SSA抗体阳性1例,所有患者均有结节病和干燥综合征的组织病理学证据支持诊断.文献复习41例（包括本组报道的4例）,其中女性37例,男性4例,眼干40例,口干38例,肺门、纵隔淋巴结肿大28例,间质性肺炎15例,有呼吸道症状13例,抗核抗体阳性23例,抗SSA抗体阳性19例,抗SSB抗体阳性10例,类风湿因子阳性12例,所有患者均有两种疾病的组织病理学证据.结节病并存pSS时有多系统受累、自身抗体阳性,但最终确诊还需组织病理学依据.

超声评分法诊断干燥综合征涎腺病变

目的 研究超声评分法对干燥综合征涎腺病变的诊断价值.方法 由两名医师对103例腮腺和颌下腺4个腺体的声像图进行评分,进行统计分析确定诊断最佳阈值及其诊断效力.结果 两名医师评分结果的Kappa值为0.80.疾病组腮腺、颌下腺评分和总评分均明显高于对照组.腮腺、颌下腺评分和总评分的ROC曲线下面积分别为0.98、0.95、0.99,总评分的最佳诊断阈值为8,诊断敏感性、特异性、阳性预测值和阴性预测值分别为93%、97%、95%、95%.结论 腮腺和颌下腺4个腺体的超声评分法评价干燥综合征涎腺病变具有较高的诊断价值.

原发性干燥综合征继发肺间质病变的临床特点

目的 探讨原发性干燥综合征（pSS）继发肺间质病变（ILD）的临床、实验室及病理特点.方法 收集我院2006-2008年住院的15例pSS-ILD的临床资料,与同期住院的18例pSS无ILD进行比较.其中8例pSS-ILD有随访,观察治疗后胸部高分辨CT（HRCT）的变化情况.结果①pSS-ILD的发病年龄[（57±11）岁]比pSS无ILD[（43±11）岁]晚（P〈0.01）.6例 pSS-ILD患者首发症状为咳嗽、咯痰、胸闷和（或）活动后气促,出现呼吸道临床表现、心脏受累及肺动脉高压（PAH）较pSS无ILD明显增多（P〈0.01）.②pSS-ILD血清免疫球蛋白G（IgG）水平[（23±8）g/L]比pSS无ILD[（17±5）g/L]明显增高（P〈0.01）.③pSS-ILD胸部HRCT常见网格状、条索状、结节状影,8例胸膜受累,蜂窝状改变常见（5例）,3例出现PAH.8例患者治疗6个月,4例胸部HRCT吸收好转,2例无明显变化,2例病变进展.④病理常见肺泡壁及肺泡组织局灶性纤维化,肺泡腔内有炎细胞浸润,间质多灶性淋巴细胞浸润,1例患者符合非特异性间质性肺炎（NSIP）改变.结论 pSS-ILD的发病年龄较大,易出现呼吸道临床表现,心脏受累及继发PAH,血清IgG水平高.1/3患者HRCT可见蜂窝状改变,多数患者治疗后病变吸收好转.病理可见NSIP改变.

原发性干燥综合征合并恶性淋巴瘤的临床特征

目的 观察和了解原发性干燥综合征（pSS）患者发生恶性淋巴瘤（ML）的特点,探讨危险因素.方法 1980年1月至2010年8月在北京协和医院住院的pSS合并ML的患者（pSS/ML）共17例,进行回顾性分析 同期未合并ML的pSS患者（pSS/nML）共4485例,随机抽取163例进行比较.结果 （1）17例pSS/ML患者中女14例,男3例 平均年龄（53±13）岁,自发病至确诊pSS（8±9）年,自pSS确诊至ML确诊平均间隔（4±4）年.男女比例、发病年龄、病程与pSS/nML组的差异无统计学意义（P＞0.05） （2）pSS/ML与pSS/nML临床表现和实验室检查差异有统计学意义（P＜0.05）的有：淋巴结肿大、腮腺肿大和白细胞降低 （3）17例pSS/ML患者,15例为非霍奇金淋巴瘤（NHL）（其中B细胞来源14例）,1例为霍奇金淋巴瘤（HL）,1例为T细胞来源淋巴肉瘤.结论 pSS患者随着病程延长,有腮腺肿大、淋巴结肿大、白细胞降低等表现的更容易合并ML,且以NHL为主,预后较差.