Objective To investigate the association of fluctuation of anticardiolipin antibody (ACA) levels and clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods Anticar-diolipin antibodies were measured sequentially by commercial enzyme-linked immunosorbent assay (ELISA) in 85 SLE patients. Patients were classified into two groups: group A was persistently positive for ACA, group B was transiently positive for ACA, and the clinical features of the two groups were compared. Results There were 37 patients (44%) in group A, and 48 (57%) patients in group B. 41% patients had occurred thromboeytopenia in group A, 19% patients in group B, the difference was significant (P<0.05); platelet accounts were (24±6)×109/L in group A,and (46±10)×109/L in group B, the difference was significant (P< 0.05), too. 11% patients experienced thrombosis in group A, and none in group B, the difference was significant (P<0.05). 19% in group A and 4% in group B had occurred valvular diseases, the difference was significant (P<0.05.). The prevalence of lupus anticoagulant was 32% in group A, 13% in group B and the difference was significant (P<0.05). There was no significant difference between the two groups in Raynaud's phenomenon, pulmonary hypertension, and lupus nephritis (P0.05). Conclusion Fluctuations of anticardio-lipin antibodies are asso-ciated with thrombosis, thrombocytopenia vascular disease and lupus anticoagulant however, there is no lack of association with other clinical manifestations in SLE patients.

Objective The aims of this study were to compare the clinical and laboratory responses to ursodeoxycholic acid (UDCA) monotherapy with the combination therapy of UDCA plus prednisolone/azathioprine in primary biliary cirrhosis(PBC),and to investigate the risk factors affecting the therapeutic responses.Methods Eighty-two patients with untreated PBC were divided randomly into three groups.Group U (28 patients) received UDCA alone,group UP(27 patients) received UDCA and pr ednisolone,while group UA (27 patients ) received UDCA and azathioprine.The clinical and laboratory data were recorded after treated for 3,6 and 12 months.Repeated measures ANOVA and COX regression model were used for statistical analysis.Results Fatigue and pruritus were improved only in group UP(P=0.015 and P=0.037 respectively).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),gamma-glutamyl transferase (GGT),total bilirubin (TBIL),direct bilirubin (DBIL) and IgM in the 3 groups were decreased (P＜0.05),while there was no statistical significant difference between the three groups (P＞0.05).The patients with disease progression had higher Mayo risk score (MRS) (P=0.018) and prolonged prothrombin time (PT)(P=0.042).In group UP,side-effect associated with glucocorticosteroids occurred in eight patients while there was no side-effect in group U.High baseline levels of ALP、GGT and CHO were risk factors for biochemical remission(P=0.015).The increase of DBIL,TBIL,total bile acid(TBA) and PT did not contribute to the prediction of biochemical remission ( P=0.075 ).Conclusion There are no differences among the three groups in the improvement of hepatic biochemical data and IgM.The combination therapy of UDCA with prednisolone could relieve fatigue and itching.The disease of patients with higher Mayo risk score and prolonged PT tend to progress.High baseline levels of ALP,GGT and CHO are risk factors for biochemical remission.High baseline levels of TBIL,DBIL,TBA and PT could not predict biochemical remission.The incidence of adverse effect is lowest when treated with UDCA alone.

Three female patients admitted with elevated creatine kinase,impaired muscle on electromyogram,and positive repetitive nerve stimulation and neostigmine tests were diagnosed as polymyositis (PM) with myasthenia gravis (MG).Twenty five more cases were retrieved by literature search,and the clinical data of total 28 cases were analyzed.There were 10 males and 18 females with an average age of 56 years.The clinical manifestations include dyspnea(43％),dysphagia(43％),ptosis (43％),dysarthria(29％),diplopia(18％),cough after drinking(14％),myalgia(11％).Thirteen out of 26 cases (50％) had positive results in repetitive nerve stimulation (RNS) and 10/11 showed positive reaction in neostigmine test.Serum positive anti-acetylcholine receptor was detected in 21 out 23 patients (91％).

Objective To generate an autoimmune cholangitis animal model and investigate whether CXCR3 and its ligand were involved in the pathogenesis of primary biliary cirrhosis (PBC). Methods Female C57BL/6 wild-type (WT) mice and CXCR3 knockout (CXCR3-/-) mice were injected with 5 mg/kg of poly I:C intra-peritoneally twice a week for 24 consecutive weeks. Liver specimens were collected to evaluate the degree of cell infiltration. AMA was assayed by ELISA. Differences in pathology were compared between CXCR3-/- mice and wild-type. Student's test was used to assess the differences. Results Anti-mitochon-drial antibody (AMA) and alkaline phosphatase (ALP) level were elevated significantly in the sera of all poly Ⅰ:C injected mice compared with control mice. AMA titers in serum were increased in the poly I:C injected WT mice compared with that of the control mice at week 8, 16, and 24 respectively (0.70±0.41 vs 0.17±0.04,0.48±0.35 vs 0.19±0.07, 0.69±0.44 w 0.20±0.06, P＜0.01). There was no significant difference between AMA titers in the serum of WT PBC mice and CXCR3-/- PBC mice (0.70±0.41 vs 0.56±0.25, 0.48±0.35 vs 0.46±0.35, 0.69±0.44 vs 0.85±0.34). Serum alkaline phosphatase (ALP) levels were raised among the poly I:Cinjected WT mice compared with WT controls (115±33) vs (65±7) U/ml; (119±32) vs (70±9) U/ml; (133±52) vs (77±10) U/ml. The serum ALP levels in CXCR3-/- PBC mice were (106±29), (112±29)and (122±60) U/ml at week 8, 16 and 24 respectively. There was no significant difference in ALP level between WT and CXCR3-/- mice PBC model. Considerable numbers of infiltrating cells were detected at the portal areas 8weeks after poly I:C injection, which progressed up to 24 weeks. At week 24, the interlobular bile ducts were lost and bile-plug were evident. Compared to WT mice model, this results revealed that CXCR3-/- mice, had fewer foci of inflammation and significant reduction in total inflammatory cells in their livers than those of the WT mice at 8, 16 and 24 weeks after injection of poly I:C. At week 24, there were no cholestasis orgranulomas in CXCR3-/- mice of PBC models. Compared to the control model, CXCL10 serum level was increased in PBC model. With the disease progression, CXCL10 serum level was elevated gradually. In comparison with wild mice, CXCR3-/- mice model had a higher serum level of CXCL10. At week 24, there was significant difference of CXCL10 serum level between wild-type mice and CXCR3-/- mice model. Conclusion In conclusion, these findings indicate that, CXCR3-/- mice might have a delayed onset and ultimately could not recruit sufficient effector cells to the liver for inflammation development.

Objective To generate an primary biliary cirrhosis animal model and investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC).Methods Female C57BL/6 wild-type(WT)mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 consecutive weeks.Establishment of PBC was confirmed by liver function test,serom autoantibodies and liver biopsy.Expression of CXCR3 on lymphocytes of liver/spleen and level of CXCL10 in peripheral blood were tested by flow cytometry assay and ELISA.The t-test was used for two group data comparison.Results Anti-mitochondrial antibody was detected in the sera of all poly I:C injected wild type C57BL/6mice.Considerable numbers of inflammatory cells were detected at the portal areas 8 weeks after the initiation of poly I:C injection,which progressed up to 24 weeks.Compared the to control mice,serum level of CXCL10was increased in PBC mice.With the disease progression,CXCL10 serum level was elevated.The level of CXCL10 at 8,16 and 24 weeks in PBC model was 0.28±0.10,0.33±0.19 and 0.27±0.11,which were much higher than those of the control mice.CXCL10 serum level of control mice was 0.07±0.03.0.08±0.05,0.10±0.04 respectively.Compared to control model,the proportion of CXCR3+ positive cells was inereased in the intrahepatic infiltrates of PBC model,mostly on CD8+ T cells.Moreover,the expression of CXCR3 was decreased in CD3+and CD8+splenocytes from PBC model compared with control model.Conclusion CXCR3and CXCL1O may attract T cells to the liver of PBC mice mode in the process of PBC development

The clinical data were collected from medical record of 749 patients admitted into Peking Union Medical College Hospital from January 2008 to March 2013.They were diagnosed with primary Sj(o)gren's syndrome (PSS) at discharge.Clinical manifestations,laboratory results and outcomes were compared between PSS patients with pulmonary hypertension (PSS-PH) and those without (PSS-non PH).PSS-PH group had higher proportions of Renault phenomenon (36.8％ vs.20.0％,P =0.05),pericardial effusion (55.3％ vs.0.0％,P＜0.01),leukocytopenia (42.1％ vs.30.0％,P =0.03),elevated IgG level [(28.8 ±11.2) vs.(21.5 ±10.0) g/L,P=0.01] and hypothyroidism(34.2％ vs.12.5％,P=0.05) with significant significance.The PSS patients had leukocytopenia low thyroid function,rising IgG and pericardial effusion with pulmonary hypertension.

Objective:To investigate the function of gasdermin D (GSDMD) in intestinal damage of mice with severe acute pancreatitis (SAP).Methods:The healthy C57BL/6 mice were divided into four groups randomly, including normal saline (NS) group, small interfering RNA (siRNA)-NS group, SAP model group and siRNA-SAP group, with 6 mice in each group. The SAP mouse model was reproduced by intraperitoneal injection of caerulein 50 μg/kg combined with lipopolysaccharide (LPS) 10 mg/kg; the NS group was given the same amount of NS; in the siRNA-SAP group and siRNA-NS group, siRNA 50 mg/kg was injected through the tail vein three times before modeling or injection of NS. The blood of mice eyeball in each group was taken 12 hours after modeling, and serum interleukins (IL-1β, IL-18) levels were detected by enzyme linked immunosorbent assay (ELISA). The mice were sacrificed to observe the general changes in abdominal cavity, the pancreas and ileum tissues were taken to observe the pathological changes under a light microscope. The expression of long-chain non-coding RNA uc.173 (lnc uc.173) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect the expression of tight junction proteins zonula occluden-1 (ZO-1) and Occludin in intestinal mucosal epithelial cells. Western blotting was used to detect the GSDMD protein expression level in the intestinal tissue.Results:The serum levels of IL-1β and IL-18 in the SAP model group were significantly higher than those in the NS group and the siRNA-NS group [IL-1β (ng/L): 146.66±1.40 vs. 44.48±5.76, 81.49±10.75, IL-18 (ng/L): 950.47±177.09 vs. 115.43±16.40, 84.84±21.90, all P < 0.05]; and the levels of IL-1β and IL-18 in the siRNA-SAP group were significantly lower than those in the SAP model group [IL-1β (ng/L): 116.26±15.54 vs. 146.66±1.40, IL-18 (ng/L): 689.96±126.08 vs. 950.47±177.09, both P < 0.05]. General observation showed that there were no obvious abnormalities in the abdominal cavity of the mice in the NS and siRNA-NS groups; the mice in the SAP model group and the siRNA-SAP group had different degrees of edema and congestion in the intestine; compared with the SAP model group, the abnormalities in the siRNA-SAP group was significantly reduced. Under light microscope, there were no obvious changes in the pancreas and intestinal mucosa in the NS group and the siRNA-NS group; the pancreatic tissue of the SAP model group and the siRNA-SAP group had different degrees of edema, inflammatory cell infiltration, and lobular structure damage, and the intestinal mucosa was damaged to a certain degree, and the villi were broken to varying degrees, but the damage in the siRNA-SAP group was lighter. The results of RT-PCR showed that the expression of lnc uc.173 in the intestinal tissues of the model SAP group was significantly lower than that of the NS group and the siRNA-NS group (2 -ΔΔCt: 0.26±0.12 vs. 1.01±0.37, 0.67±0.32, both P < 0.05), while the expression of lnc uc.173 in the siRNA-SAP group was significantly higher than that in the SAP model group (2 -ΔΔCt: 0.60±0.39 vs. 0.26±0.12, P < 0.05). Immunohistochemistry showed that ZO-1 and Occludin proteins in the NS group were distributed along the epithelial cells of the intestinal mucosa, showing a strong expression; ZO-1 and Occludin expressions were significantly reduced in the SAP model group and siRNA-SAP group, but the expressions in the siRNA-SAP group was higher than that in the SAP model group. Western blotting showed that the expression level of GSDMD protein in the intestinal tissues of the SAP model group was significantly higher than that of the NS group and the siRNA-NS group [GSDMD protein (GSDMD-N/β-actin): 1.99±0.46 vs. 1, 1.00±0.78, both P < 0.05]. Compared with the SAP model group, the expression of GSDMD protein in the siRNA-SAP group was significantly decreased [GSDMD protein (GSDMD-N/β-actin): 1.42±0.42 vs. 1.99±0.46, P < 0.05]. Conclusions:The systemic inflammatory response and intestinal mucosal barrier damage of SAP mice may be related to the increase of GSDMD expression in intestinal tissues. GSDMD mediates cell pyrolysis to promote the release of inflammatory factors, cause intestinal injury, and down-regulate the expression of intestinal epithelial cell tight junction proteins such as ZO-1 and Occludin, resulting in intestinal mucosal damage.

The clinical data of 13 patients diagnosed as Takayasu's arteritis with cardiomyopathy in Peking Union Hospital were reviewed.Echocardiography showed cardiomegaly (left chambers mainly),diffuse weakened myocardial wall movement and reduced left ventricular ejection fraction.Dilated cardiomyopathy was diagnosed in two patients.Glucocorticoid and cyclophosphamide were the essential medication for treatment.One patient died,1 patient was aggravated and the disease condition in remaining 11 patients was stable or improved.Takayasu's arteritis with cardiomyopathy is a rare disease and it attacks younger people.It is difficult to identify at onset,and the disease deteriorates rapidly.Echocardiography should be performed earlier to evaluate the heart function for early diagnosis and treatment.Administration of large dose of glucocorticoid and cyclophosphamide at early stage may improve the prognosis.

ObjectiveTo investigate the changes of major causes of death of patients with systemic lupus erythematosus(SLE).MethodsDeath cases with SLE from January 1986 to May 2011 in Peking Union Medical College Hospital were retrospectively analyzed.ResultsOut of 3554 patients with SLE,252 patients died,including 223 women and 29 men.The mortality rate was 7.2％ among female and 6.2％ among male,the overall mortality rate was 7.1％.The mortality rate in SLE patients had dropped steadily in the past 25 years,but there was a mild increase of mortality in 2006-2011 compared with that in 2001-2005 (5.7％vs 5.3％ ).In addition to infection,neuropsychiatric lupus and lupus nephritis had become the most common causes of death in SLE patients during the past 25 years.Furthermore,diffuse alveolar hemorrhage,severe pulmonary hypertension,coronary heart disease,thrombocytopenia,interstitial lung disease,lupus pneumonia,gastrointestinal hemorrhage, intestinal obstruction and multiple organ failure were the common causes of death,accounting for 4.4％,4.4％,3.2％,2.8％,2.4％,2.0％,2.0％,1.2％ and 1.2％ of all the death cases respectively.From 1986 to 2005,infection,neuropsychiatric lupus and lupus nephritis were the most common causes of death in patients with SLE,whereas the cases dying from lupus nephritis had decreased obviously and severe pulmonary hypertension had become the third most frequent causes of death during the past 5years.From 1986 to 1990,lupus nephritis,infection and neuropsychiatric lupus accounted for 31.4％,25.7％and 25.7％ of death cases respectively.From 1991 to 1995,lupus nephritis,infection and neuropsychiatric lupus accounted for 27.6％,24.1％ and 24.1％ respectively.From 1996 to 2000,infection,neuropsychiatric lupus and lupus nephritis took up 31.6％,21.1％ and 15.8％ respectively.From 2001 to 2005,infection,neuropsychiatric lupus and lupus nephritis took up 34.9％,20.6％ and 7.9％ respectively.From 2006 to 2011,infection, neuropsychiatric lupus and pulmonary hypertension accounted for 60.3％, 11.8％ and 7.4％ respectively.The mortality in the first year was the highest in the whole disease course,accounting for 32.5％ of patients.Deaths caused by neuropsychiatric lupus and infection happened most frequently during the first year,accounting for 41.9％ and 32.9％,whereas deaths caused by lupus nephritis occurred most frequently 10 years later,accounting for 32.3％.Age and gender had significant association with the major causes of death.The male patients took up 50.0％ of the total patients dying from coronary heart disease,in which 75.0％ of patients were older than 50 years.ConclusionInfection,neuropsychiatric lupus and lupus nephritis are the three most common causes of death in SLE patients fron 1986 to 2005.Severe pulmonary hypertension has become the third most frequent causes of death during the past 5 years instead of lupus nephritis.Severe infection has increased significantly and has been the leading cause of death in SLE patients in recent 5 years.

Objective To assess the clinical features of primary biliary cirrhosis(PBC)associated with systemic sclerosis(SSc)in order to facilitate recognition of this overlap syndrome(SSc-PBC). Methods The clinical data of 9 patients with SSc-PBC in Peking Union Medical College Hospital were retrospectively studied with literature review. Results ① Nine patients including 8 female were at a mean age of(54±8)years. Sevene patients initially presented with SSc and developed PBC over(4.3±2.3)years. ② Eight patients were diagnosed limited cutaneous SSc(leSSc), which included 7 patients with CREST syndrome. The most frequent manifestations were Raynaud's phenomenon(8/9)and esophageal dysfunction(8/9). Four patients with PBC manifested subclinically, but laboratory results revealed increased ALP/GGT in most patients(8/9).Two patients received liver biopsies, which confirmed the diagnosis of PBC. ③ Antinuclear antibodies(ANA)and anti-mitochondrial antibody(AMA)were detected in all the patients, among them, 8 with positive anticentromere antibody(ACA)and 8 with positive AMA-M2. ④ UDCA and glucocorticosteroid might help early stage patients with SSc-PBC, but lack efficacy in patients complicated with interstitial lung disease, pulmonary hypertension or cirrhosis. Conclusion PBC might be overlapped with SSc, especially lcSSc(CREST syndrome). Screening of autoantibodies, such as ACA, AMA and AMA-M2, could help rheumatologists early recognition of SSc-PBC and improve the prognosis of this overlap syndrome by early intervention.