Search

To explore the activation of hypomethylated DNA on plasmacytoid dendritic cells (pDC) in patients with systemic lupus erythematosus (SLE).Peripheral blood mononuclear cells (PBMC) were isolated from whole blood of SLE patients and healthy controls. The methylation level of DNA and the expression of DNA methyltransferase 1 (DNMT1) mRNA were detected. Flow cytometry was used to detect the expression of CD32 on pDC and the serum concentration of interferon-alpha (IFN-α) measured by enzyme-linked immunosorbent assay (ELISA).The DNA methylation level from SLE patients (1.4 ± 0.6) % was lower than that of controls (1.8 ± 0.7) % (P0.01). The expression of DNMT1 mRNA significantly decreased in SLE patients (0.06 ± 0.03) versus the controls (0.09 ± 0.02) (P0.01). The CD32 expression on pDC from SLE patients (29 ± 19)% was higher than that from controls (18.02 ± 7.80)% (P0.01). The serum level of IFN-α in SLE patients (4.5 ± 6.7) ng/L was significantly higher than that of controls (2.1 ± 2.0) ng/L (P0.01). The methylation level of DNA in SLE patients was positively correlated with the expression of DNMT1 mRNA (r = 0.257, P0.05) and negatively with the expression of CD32 (r = -0.358, P0.01) and IFN-α (r = -0.280, P0.05).The methylation level of genomic DNA decreases in SLE patients due to the down-regulated expression of DNMT1 gene. Hypomethylated DNA may be translocated intracellularly via endocytic receptor (CD32) on pDC. And the activation of pDC is induced to produce IFN-α so as to participate in the onset of SLE.

To explore the effects of transcription factor ETS-1 mRNA and B lymphocyte-associated cytokines on the differentiation of B cells in systemic lupus erythematosus (SLE) patients and explore its pathogenic and clinical significance.Thirty-one SLE patients (20 active and 11 inactive) and 15 healthy controls were enrolled. CD19+ B cells were isolated with magnetic beads. The levels of ETS-1 mRNA in B cells were determined by real-time polymerase chain reaction (PCR). Flow cytometry was used to detect the altered ratio of CD19-CD138 + plasma cells and CD19 + B cells. And enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum levels of B cell differentiation-related cytokines interleukin-10 (IL-10) and APRIL.Compared to the healthy controls, SLE patients showed decreased mRNA expression level of ETS-1 in B cells (Z = -4.218, P0.01) . Moreover, the expression level of ETS-1 mRNA was significantly negatively correlated with the proportion of CD19-CD138+ plasma cells (r = -0.359, P0.05) and negatively correlated with the CD19-CD138 +B cells/CD19+ plasma cells ratio (r = -0.493, P0.01) . However, there was no correlation in normal controls. Significant negative correlation existed between the expression level of ETS-1 mRNA in B cells and the serum levels of IL-10 and APRIL in active SLE patients. But no correlation existed in inactive group.ETS-1 may participate in the pathogenesis of SLE through its effects on the differentiation of B cells and cooperation with IL-10 and APRIL.

To evaluate the early diagnostic value of matrix metalloproteinase-9 (MMP-9) level on admission for ST-segment elevation myocardial infarction (STEMI), explore the relationship between MMP-9 and global registry of acute coronary events (GRACE) scores and determine the values of MMP-9 in short-term prognosis of STEMI.A total of 55 STEMI patients admitted into our hospital between September 2011 and February 2012 were recruited. There were early STEMI (≤ 4h of onset, n = 22) and late STEMI (4 h after onset, n = 33). Fifty subjects of coronary artery without significant stenosis after angiography were enrolled into a control group. The plasma levels of MMP-9 in venous blood were detected with enzyme-linked immunosorbent assay (ELISA). And the GRACE risk score was used for risk assessment. The incidence of new or recurrent myocardial infarction, target vessel revascularization, cardiac death, heart failure (MACE) was recorded during a follow-up period of 6 months.The MMP-9 levels were significantly higher in patients with STEMI (P0.001), early STEMI (P0.001) and late STEMI (P0.001) than the control group. And no statistical differences existed between early STEMI and late STEMI (P0.05). The level of MMP-9 was positively correlated with the GRACE risk score. MACE occurred in 8 [14.5% (8/55)] patients during hospitalization and 17 [30.9% (17/55)] patients during follow-up. Receiver operating characteristic (ROC) curve analysis showed area under the curve (AUC) of on admission GRACE risk score and MMP-9 levels were 0.848 (95%CI 0.706 - 0.991, P = 0.002) and 0.766 (95%CI 0.575 - 0.957, P = 0.017) respectively. ROC curve analysis showed AUC of hospital discharge GRACE risk score and MMP-9 levels were 0.737 (95%CI 0.601 - 0.873, P = 0.005) and 0.711 (95%CI 0.565 - 0.856, P = 0.013) respectively. No statistical differences existed between GRACE risk score and MMP-9 levels for predicting the short-term risk of MACE (P0.05).The plasma level of MMP-9 has a higher diagnostic value for early STEMI. Positively correlated with the GRACE risk score, it is a predicator of short-term risk of MACE.

To detect the expression of B7-H4 in salivary gland and sera in patients with primary Sjogren's syndrome (pSS).A total of 40 pSS patients were referred to our department from June 2009 to January 2011. Immunohistochemistry and flow cytometry were used to detect the expression of B7-H4 in salivary gland from pSS patients and disease controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect soluble B7-H4 of serum from pSS patients and healthy donors.Immunohistological staining revealed that B7-H4 antigen was restricted to tubular epithelium. The B7-H4 positive expression of tubules in salivary gland biopsies from pSS patients (18 ± 14)% were lower than that of controls (85 ± 13)% (P0.05). Flow cytometry revealed that the B7-H4 expression of cell suspensions from salivary gland from pSS patients (42 ± 21)% were lower than that of controls (48 ± 22)% (P0.01). And the serum level of soluble B7-H4 detected in pSS patients (49 ± 31)µg/L significantly decreased than that in healthy donors (71 ± 27) µg/L (P0.05) and positively correlated with saliva and tear flow rates (P0.01) respectively.The expression of B7-H4 molecule may play some roles in the progression of pSS. And a further understanding of its mechanism helps to elucidate the pathogenesis of pSS.

To explore the clinical features, predictive factors and unfavourable prognostic factors of interstitial lung disease (ILD) in the patients with polymyositis and dermatomyositis (PM/DM) so as to provide rationales for early clinical diagnosis and treatment.The medical records of 244 PM/DM patients from Department of RheumatologyImmunology of Anhui Medical University Affiliated Provincial Hospital from August 2001 to August 2011 were reviewed to analyze the clinical features, predictive factors and unfavourable prognostic factors of ILD in PM/DM patients.The major clinical manifestations of PM/DM-ILD included dry cough, chest tightness and shortness of breath during activities and Velcro rale in lower lung. Besides anti-Jo-1 antibody, multivariate unconditional Logistic regression analysis indicated that amyopathic dermatomyositis (ADM), arthralgia/arthritis, fever and Gottron's sign were the predictive factors for the development of ILD in PM/DM patients. ADM and Hamman-Rich-like pattern ILD were the poor prognostic factors while large dose glucocorticoids plus immunosuppressant therapy in the early time was a protective factor for PM/DM-ILD patients.Some clinical features are the predictive factors for the development of ILD. ADM and Hamman-Rich-like pattern ILD are poor prognostic factors. Large dose glucocorticoids plus immunosuppressant therapy can significantly improve the prognosis of PM/DM patients.

To explore the distribution characteristics of apolipoprotein A5 (ApoA5) gene c.553GT polymorphism and the relationship of serum lipid in Chinese Han and Uighur populations in Xinjiang, China.The genotypes of ApoA5 gene c.553GT polymorphism were detected in 406 Uighur and 527 Han people by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).The frequencies of GG, GT and TT genotypes of ApoA5 gene c.553GT were 378 (93.1%), 27 (6.7%) and 1 (0.25%) patients in Uighurs versus 478 (90.7%) patients, 49 (9.3%) patients and 0% in Hans. There was no significant difference in the distribution of genotypes between two groups (P0.05). In both groups, individuals with T allele (TT + GT genotype) had a higher level of serum triglyceride than those with GG genotype. After adjusting for gender, age, smoking, alcoholism, body mass index, blood pressure and blood lipid, non-conditional logistic regression analyses revealed that individuals with T allele (TT + GT genotype) in both groups had an elevated risk of HTG versus the GG genotype (OR = 3.31, 95%CI: 1.31 - 8.36 in Uighurs vs OR = 3.98, 95%CI: 1.81 - 8.74 in Hans).The mutation of c.553GT polymorphism of ApoA5 gene is associated with the level of serum triglyceride in Uighur and Han populations of Xinjiang. And T allele may be a risk factor of hypertriglyceridemia.

To investigate the prevalence and risk factors of smoking and metabolic syndrome (MS) among male Uygur and Kazakh adults residing in Xinjiang.Four-stage selected random sampling was used to analyze the prevalence and the relationship between the risk factors of smoking and metabolic syndrome. The sampled adult populations over 35 years old were collected 6 localities (Urumqi, Kelamayi, Fukang, Turfan Basin locality, Hetian localityYili Kazakh Autonomous Prefecture) in Xinjiang, China. The subjects were 4019 males of Uygur and Kazakh. Each individual answered a questionnaire, received physical examinations and a biochemical indicator survey. The smoking patients were divided into two groups: one complicated with metabolic syndrome and the other not. A logistic regression analysis was also made to identify the possible risk factors and their powers on the prevalence of metabolic syndrome with smoking.With regards to the habit of smoking, the smokers of Uygur and Kazakh were 869 and 1114 respectively. The prevalence of MS was 24.74% and 29.62% for Uygur and Kazakh smokers respectively. And 16.75% and 24.72% for Uygur and Kazakh non-smokers respectively. The comparison of baseline information showed that, in Uygur males, the mean values of diastolic blood pressure, waist circumference and triglyceride were higher in smoker group than those in non-smoker group (P0.05); in Kazakh males, the mean values of systolic blood pressure, diastolic blood pressure and waist circumference were higher than nonsmoker group (P0.05). Logistic regression analysis showed that the OR value of smoking was 1.698 (95%CI 1.129 - 2.553) in Uygur and 1.845 (95%CI 1.544 - 2.206) in Kazakh of MS patients.The prevalence of MS is higher in male smokers than that in non-smokers in Uygur and Kazakh. Perhaps smoking is one of the risk factors for MS.

To investigate the detection rate of carotid artery plaque in Han, Uygur and Kazakh adult populations of Xinjiang.During the period of October 2007 to March 2010, the present study was performed in 13896 Han, Uygur and Kazakh adults of Xinjiang aged 35 years old and over by a four-stage random sampling method. All subjects were investigated by a standardized questionnaire, physical, biochemical examination and ultrasonography of carotid arteries. Risk factors were analyzed by a logistic regression model.The prevalence of carotid artery plaque was 10.2%. After standardization, the detection rate of Chinese Han, Uygur and Kazakh populations was 2.46%, 2.31% and 1.84% respectively. By the analysis of multivariate logistic regression, age (OR 1.032, 95%CI 1.026-1.037), smoking (OR 1.358, 95%CI 1.164-1.585), total cholesterol (OR 1.075, 95%CI 1.018-1.135), blood glucose (OR 1.050, 95%CI 1.020-1.081) and systolic blood pressure (OR 1.011, 95%CI 1.008-1.014) were independent risk factors in the occurrence of carotid artery plaque. Females (OR 0.653, 95%CI 0.545-0.738) and high-density lipoprotein (OR 0.864, 95%CI 0.751-0.994) were the protective factors in the occurrence of carotid artery plaque.The detection of carotid artery plaque in Xinjiang increases substantially with age and difference exists between nationalities. The associated risk factors of the formation of carotid artery plaque include gender, age, smoking, high-density lipoprotein, total cholesterol, blood glucose and systolic blood pressure. The effect of these factors is different between genders.

To investigate the prevalence and distribution pattern of hypertension in Xinjiang adult population.A total of 15,061 adults at 35 years old or over were surveyed. Four-stage selected random sampling was employed to analyze the prevalence and distribution pattern of self-reported congestive hypertension in different groups of nationality, age and gender. The sampled adult population was collected from 7 localities (Urumqi, Ke lamayi, Fukang, Turfan Basin, Hetian, Altay, Yili Hazakh autonomous prefecture) in 23 municipalities and 5 autonomous counties in Xinjiang. The proportion of male to female was 50% each.The prevalence of hypertension was 36.21% (male: 38.70% vs female: 34.22%). The Prevalence of hypertension was 33.42%, 28.50% and 48.69% in Han, Uygur and Hazakh populations respectively. The prevalence of hypertension was higher in Hazakh than Han people (χ2=29.36, P0.01). The males had a higher frequency of hypertension than the females (χ2=20.01, P0.01). The risk of hypertension increased substantially with age. The analysis of multiple logistic regression revealed that age (OR=1.06), alcohol consumption, obesity (OR=3.12) and levels of triglyceride (OR=1.30) and cholesterol (OR=1.32) and serum glucose (OR=1.41) were risk factors of hypertension. The corresponding relative hazards were age, alcohol consumption, obesity and levels of triglyceride and cholesterol and serum glucose for Han; the risk factors were similar in Uygur except serum glucose. Age, obesity and levels of triglyceride were only for Hazakh.There is still a higher prevalence of hypertension in Xinjiang. The prevalence of hypertension increases substantially with age and there is difference between different nationalities.

To investigate the prevalence of peripheral arterial disease (PAD) and its correlative risk factors in Xinjiang Uygur and Kazak adult populations.The subjects over the age of 35 years old in Urumqi, Karamay City, Fukang City, Turpan Region, Hotan Prefecture and Yili Kazak Autonomous Prefecture were selected by the four-stage random sampling method. The investigators collected the data of PAD prevalence in different nationalities, different age groups and different gender groups and analyzed its risk factors.The prevalence of PAD in Uygur and Kazak adults was 6.46% (n = 542). The standardized prevalence was 6.51%. The prevalence of PAD was 7.05% (n = 315) in Uygur adults and 5.79% (n = 227) in Kazak adults. The standardized prevalence in the Uygur and Kazak adults was 7.08% and 5.83% respectively. The prevalence of PAD of different nationalities was different (χ(2) = 5.55, P0.05). And its prevalence was 4.49% (n = 170) in males and 8.08% (n = 372) in females. The standardized prevalence was 4.30% in males and 7.90% in females. The prevalence of PAD in males and females was significantly different (χ(2) = 44.26, P0.01). The multivariate logistic regression analysis was performed. Age (OR = 1.01, 95%CI 1.00 - 1.02), females (OR = 1.75, 95%CI 1.45 - 2.14), overweight or obesity (OR = 1.04, 95%CI 1.01 - 1.06), diabetes (OR = 1.59, 95%CI 1.01 - 2.36), elevated systolic blood pressure (OR = 1.02, 95%CI 1.01 - 1.03), elevated diastolic blood pressure (OR = 1.08, 95%CI 1.01 - 1.11) and history of coronary heart disease (OR = 1.69, 95%CI 1.14 - 2.50) were associated with an elevated prevalence of PAD.The prevalence of PAD is lower in Xinjiang Uygur and Kazak adult populations. Females, age, overweight or obesity, diabetes, elevated systolic blood pressure and a history of coronary heart disease are risk factors of PAD.

To explore the association of genetic polymorphism (rs12218) of serum amyloid protein A1 (SAA1) with serum high density lipoproteins cholesterol (HDL-C).A total of 607 healthy subjects were recruited into the Cardiovascular Risk Survey between June 2007 and March 2009. Their genotypes of SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).There was no significant difference between each genotype of SAA1 in triglyceride, total cholesterol and low density lipoprotein cholesterol (LDL-C). But marked significance existed between CC genotype and TT genotype in serum HDL-C level both before [(1.28 ± 0.38) mmol/L vs (1.44 ± 0.43) mmol/L, P = 0.017] and after adjusting for gender and age [(1.27 ± 0.07) mmol/L vs (1.41 ± 0.03) mmol/L, P = 0.048].In Chinese Han people, the genetic polymorphism of SAA1 may reflect the serum concentration of HDL-C. The carriers with CC genotype have a lower HDL-C level.

To investigate the characteristics of renal oxygenation status in aristolochic acids I (AA-I) induced ATN rat model by method of blood oxygenation level-dependent MRI (BOLD-MRI) and compare it with ATN model caused by gentamicin.28 male Wistar rats were randomly divided into control, AAN and GM groups, which were subcutaneously injected with normal saline, AA-I (25 mg x kg(-1)x d(-1)) or GM (200 mg x kg(-1)x d(-1)) respectively for 4 days. Intrarenal oxygenation was measured by BOLD-MRI at 4(th) day and 7(th) day. Renal histopathological changes and renal function were also observed at day 7.Serum level of creatinine and urinary NAG were obviously elevated at day 7 in AAN and gentamicin group. Diffuse tubular necrosis confined to the margin of renal cortex and medulla without edema or infiltration of inflammation cells was the main pathological finding in AAN group. BOLD-MRI revealed that renal medullar R2(*) was elevated significantly at both day 4 [(50.6 +/- 15.6)/s vs (35.6 +/- 4.3)/s, P0.01] and day 7 [(58.4 +/- 14.8)/s vs (37.8 +/- 3.6)/s, P0.01] in AAN group when compared to control, showing opposite changes to GM group whose R2(*) was decreased at the same time. In addition, the renal cortical R2(*) in AAN group was also higher than that of control [(40.3 +/- 14.7)/s vs (28.7 +/- 3.2)/s, P0.05] at day 7, showing opposite changes to GM group.Intrarenal hypoxia exists in acute AAN rats, which initiates in the medulla following an involvement in renal cortex. The phenomenon of persistent low level of intrarenal oxygenation is different from change of GM-induced ATN, which may contribute to the progression of renal interstitial fibrosis in AAN.

To investigate the level of FOXP3 expressed in CD4+ CD39+ T cells in peripheral blood of patients with systemic lupus erythematosus (SLE) and observe the regulation of glucocorticoid on it.Frequencies of CD4+ CD25+ CD39+, CD4 CD25+ FOXP3+ and CD4+ CD39+ FOXP3+ T cells and levels of FOXP3 protein were analyzed by flow cytometry of 47 SLE patients (including 29 untreated/active SLE) and 22 healthy controls. Meanwhile, correlations among three groups and influences of glucocorticoid were analyzed.Percents of CD4+ CD25+ CD39+ T cells expressed in active SLE, inactive SLE and healthy controls were (1.3 +/- 0.5)%, (1.9 +/- 0.8)% and (2.3 +/- 1.0)% respectively, the level decreased in active SLE compared with inactive SLE and healthy controls P0.05 in each group, but it had no significant difference between the latter two groups (P0.05). In active SLE, levels of FOXP3 protein expressed in CD4+ CD25+, CD4+ CD25high and CD4+ CD39+ T cells were (45 +/- 12)%, (65 +/- 14)% and (70 +/- 14)% respectively. Levels of FOXP3 expressed in CD4+ CD25high and CD4+ CD39+ T cells were higher than that expressed in CD4+ CD25+ T cells (P0.01), while it had no significant difference between CD4 CD25high T cells and CD4+ CD39+ T cells (P0.05).These results demonstrate that CD39 may be a better surface marker of regulatory T cells, and that deficiency of CD39+ Treg cells may play an important role in the pathogenesis of SLE.

To investigate the effects of ischemic postconditioning (IPost) in protecting hypertrophic myocardium subjected to ischemic-reperfusion (I/R) and to study the role of extracellular regulated protein kinase (ERK1/2) in mediating such protection.Transverse aortic constriction (TAC) operation was performed on 12-week-old C57/BL mice to establish left ventricular hypertrophy models. Sixty-four isolated TAC mouse hearts were mounted onto the Langendorff perfusion system and randomly divided into 4 equal group: (1) I/R group undergoing stable perfusion for 30 min, ischemia for 30 min, and re-perfusion for 120 min (an I/R cycle) to cause hypertrophic myocardium I/R injury, (2) IPost group undergoing ischemia for 10s and reperfusion for 10s, totally 3 cycles (60s) before reperfusion for 120 min, (3) I/R+ PD98059 (an ERK1/2 inhibitor) group undergoing perfusion of Krebs-Henseleit (KH) buffer with PD98059 10(-5)mol/L for 15 min and perfusion of KH buffer without PD98059 at the beginning of re-perfusion, and (4) IPost + PD98059 group undergoing 3 cycles of IPost and perfusion of KH buffer with PD98059 10(-5)mol/L for 15 min at the beginning of re-perfusion. Hemodynamic examination was conducted 120 min after re-perfusion to measure the left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal uprising velocity of left ventricle pressure (dp/dt(max)), and minimal uprising velocity of left ventricle pressure (dp/dt(min)). After the I/R procedure the myocardium of the left ventricle was isolated to detect the infarction size (IS). Western blotting was used to detect the protein expression of extracellular signal-regulated kinase (ERK) 1/2, phosphorylated ERK1/2, Bcl-2, Bax, and mitochondrial and cytosolic cytochrome (Cyt). C. TUNEL was used to detect the apoptotic rate.The LVSP and dp/dt(max) levels of the IPost group were (85 +/- 4) mm Hg and (3811 +/- 230) mm Hg/s, both significantly higher than those of the I/R group [(68 +/- 5) mm Hg and (2830 +/- 230) mm Hg/s respectively, both P0.05]. Compared with the I/R group, the protein levels of phosphorylated ERK1/2, Bcl-2, mitochondrial CytC of the IPost group were all significantly higher, the protein levels of Bax and cytosolic CytC, and apoptosis index were significantly lower (all P0.05), and the IS was smaller (P0.05). I/R + PD98059 showed no effects on the above-mentioned parameters. However, the results of the IPost + PD98059 group showed that in the first 15 min of reperfusion addition of PD98059 reversed all changes observed in the IPost group and eliminated the IPost protection by increasing IS to a level similar to that in the I/R group.IPost has protective effect in hypertrophic myocardium with I/R injury in vitro. ERK1/2 signaling pathway is involved in the protection of IPost by regulating the myocyte apoptosis.

To detect the new and old surface markers of regulatory T cells (Treg cells) in the CD4+ T cells of the patients with systemic lupus erythematosus (SLE) in order to reveal the role of Treg cells in the pathogenesis of SLE.Peripheral blood samples were collected from 29 newly diagnosed and treatment-naïve SLE patients, 3 males and 26 females, aged (34 +/- 13), and 24 sex and aged-matched healthy controls. Three-color flow cytometry was used to detect the CD4+CD25+ CD127(low/-) T cells, CD4+CD25high T cells, and CD4+CD25+FOXP3+ T cells. The serum anti-nuclear antibody (ANA), anti-ds-DNA antibody, anti-smooth muscle antibody, anti-nucleosome antibody, anti-C1q, C3, and C4 were detected. Blood and urine routine examinations were conducted.The proportion of blood CD4+ CD25+CD127(low/-) T cells of the SLE patients was not significantly different from that of the controls (P0.05), however, the proportions of CD4+CD25+FOXP3+ T cells and CD4+CD25high T cells of the SLE patients were 2.1 +/- 1.2 and 0.8 +/- 0.4 respectively, both significantly lower than those of the controls (4.0 +/- 1.4 and 1.8 +/- 0.8 respectively, both P0.01). The ratios of the CD4+CD25+CD127(low/-) T cells, CD4+CD25high T cells, and CD4+CD25+FOXP3+ T cells to the CD4+CD25+ T cells of the SLE patients were 0.5 +/- 0.1, 0.1 +/- 0, and 0.3 +/- 0.1 respectively, all significantly lower than those of the controls (0.6 +/- 0.1, 0.2 +/- 0.1, and 0.5 +/- 0. respectively, all P0.01). The level of CD4+CD25+CD127(low/-) T cell was positively correlated with the levels of CD4+CD25+FOXP3+ T cells and CD4+CD25high T cell (both P0.01). The levels of these 3 kinds of cells and their ratios to CD4+CD25+ T cells had no correlation with age, sex, course, IgG, IgA, IgM, urine protein, TIPU, anti-dsDNA, anti-C1q, anti-nuclear body antibody (all P0.05), however, were significantly associated negatively with SLE disease activity index, P0.05). Only the CD4+CD25+CD127(low/-) T cells/ CD4+CD25+ T cells was negatively correlated with C4 (P0.01).The relative ratio of Treg cells to the activated CD4+ T cells may play an important role in the pathogenesis of SLE.

To investigate the expression of CD(4)(+) CD(25)(+) regulatory T cells (Tregs) in the peripheral blood and salivary gland of patients with primary Sjögren's syndrome (pSS).Samples of peripheral venous blood were collected from 57 newly diagnosed pSS patients, 1 male and 56 females, aged 47 (20 approximately 76), and 46 healthy controls. The levels of CD(4)(+) CD(25)(+) T regulatory cells and CD(4)(+) CD(25)(high) T regulatory cells in the peripheral blood were measured by flow-cytometric assay. Biopsy specimens of labial gland were collected from the 57 patients and 6 healthy person or patients with labial gland cyst. Pathological examination was conducted by light microscopy. Immunohistochemistry was conducted, by using monoclonal mouse anti-human to detect the expression of CD25, CD4, CD8, and CD68. Western blotting was used to detect the levels of IgG, IgM, and IgA. The salivary flow rate was measured. Schirmer's test was used to measure the tear flow rate.The level of CD(4)(+) CD(25)(+) Tregs in the blood of pSS patients was 6.9% (2.84% - 13.50%), significantly lower than that of the healthy controls [10.9% (5.77% - 15.3%), P0.001). The level of CD(4)(+) CD(25)(high) Tregs the blood of pSS patients was 0.6% (0.001% - 1.83%), significantly lower than that of the healthy controls [1.1% (0.13% - 2.45%), P0.001]. Immunohistochemistry showed that most of the infiltrating lymphocytes in the labial gland of the pSS patients were CD(4)(+) T cells, and there was no CD(25)(+) T cell in both groups. The numbers of peripheral CD(4)(+) CD(25)(+) T cells and CD(4)(+) CD(25)(high) Tregs in the pSS patients were not correlated with the tear flow rate, salivary flow rate, anti-SS-A/SS-B antibodies, and immunoglobulin level.The pSS patients show an absence of CD(4)(+) CD(25)(+) T cell in the labial gland of pSS patients, and reduction of the numbers of CD(4)(+) CD(25)(+) and CD(4)(+) CD(25)(high) Tregs in the peripheral blood, which suggests that Tregs play an important role in the pathogenesis of salivary gland destruction in SS.

To explore the correlation of chemokines and chemokine receptors with clinical features of newly diagnosed systemic lupus erythematosus (SLE).Samples of venous blood were collected from 37 newly diagnosed SLE patients, 2 males and 35 females, aged 32.5 (15-54), and 20 healthy controls. The serum concentration of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta and reduced upon activation normal T cell expressed and secreted (RANTES) were measured by ELISA. Samples of anticoagulative serum were collected from 18 of the 37 newly diagnosed SLE patients and 10 healthy controls. The expression rates of CCR1, CCR3, and CCR5 on CD4+ T cells were detected by flow cytometry. Indirect immunofluorescence method was used to detect the anti-ds-DNA antibody, and blot immunoassay was used to detect the anti-RNP and anti-SSA antibodies. The associations of chemokines and chemokine receptors with the clinical features were analyzed.The serum concentration of MIP-1alpha of the SLE patients was (37 +/- 25) ng/L, significantly higher than that of the controls (8 +/- 9) ng/L (P0.001). The serum concentration of MIP-1beta of the SLE patients was (160 +/- 140) ng/L, significantly higher than that of the controls (76 +/- 41) ng/L (P = 0.003). The serum concentration of RANTES of the SLE patients was (184 +/- 22) ng/L, not significantly different from that of the controls (144 +/- 79) ng/L (P0.05). The serum concentration of MIP-1alpha of the SLE patients with fever was 52 ng/L +/- 27 ng/L, significantly higher than that of the SLE patients without fever (28 ng/L +/- 19 ng/L, P = 0.006). The serum concentration of MIP-1beta of the SLE patients with arthritis was 221 ng/L +/- 158 ng/L, significantly higher than that of the SLE patients without arthritis (95 ng/L +/- 83 ng/L, P = 0.008). The serum concentration of RANTES of the SLE patients with low blood platelet count was 130 ng/L +/- 122 ng/L, significantly lower than that of the SLE patients with normal blood platelet count (212 ng/L +/- 114 ng/L, P = 0.049). The percentage of CD4+ CCR3+ T cell subgroup in CD4+ T cell in peripheral blood of the SLE patients positive in anti-RNP antibody was 14.8% +/- 3.0%, significantly lower than that of the SLE patients negative in anti-RNP antibody (11.3% +/- 2.6%, P = 0.018).Abnormality of different chemokines and chemokine receptors may concern with different clinical features of SLE.

To investigate the prevalence and clinical characteristics of urinary transitional cell cancer (TCC) in uremic patients undergoing dialysis who have history of taking aristolochic acid (AA)-containing Chinese drugs.A questionnaire survey was conducted among 283 uremic patients with history of taking aristolochic acid (AA)-containing Chinese drug who were undergoing dialysis, 118 males and 165 females, aged 59 +/- 13 (22-88), to understand the drug-taking history, nephropathy-related situation, and prevalence and clinic TCC pathological features of TCC.Twenty-four of the 283 were suffering concomitant TCC with a prevalence rate of 8.48%. Sixty-six of the 283 patients had a history of taking AA-containing Chinese drugs, 22 of which had developed TCC with a prevalence rate of 33.3%, significantly higher than that among the 198 patients without a history of taking AA-containing Chinese drugs (1.0%, P0.01). Seventeen (94.4%) of the 18 TCC patients with a clear AA-taking history reported took the drug at routine doses for a long time, and 1 of the 18 patients took overdose of AA-containing drug. The average time between the beginning of taking AA-containing drugs and the occurrence of TCC was 10 years. TCC was found only in the patients with remnant urine100 ml after dialysis (8/38, 21.0%) and was not found in those with anuria after dialysis. The first symptom in the 18 TCC cases was intermittent painless hematuria. The positive rates of imageology and nuclear matrix protein (NMP)-22 detection were both more than 90%. Tumor was found in the urinary bladder or ureter (11/18, 61.2%). The relapse rate after routine surgery was 27.8%.With a very high prevalence of TCC, the patients with a history of taking AA-containing Chinese drugs should be monitored closely.

To investigate the expression patterns of MAPK family (including ERK, JNK and p38) and to analyze the effects of MAPKs on renal tubular epithelial cells (RTEC) transdifferentiation in vivo.Renal biopsy specimen were collected from 36 patients with IgA nephropathy (IgAN), which were divided into mild proliferation group (MP), focal proliferation group (FP) and proliferation-sclerosis group (PS) according to the glomerular lesions. Renal tubulointerstitial lesion score was assessed. Positive tubules of PCNA, FN, alpha-SMA, MAPK subtypes expression and phosphorylation in renal tubules were detected by immunohistochemistry staining combined with semi-quantitative method. A correlation analysis was made.In the MP, FP and PS groups of IgAN, the score of tubulointerstitial lesion, the positive stained tubule of PCNA, alpha-SMA and FN expression were more abundant with the severity of glomerular injury. The expression of alpha-SMA in tubule was correlated closely to FN expression and the score of interstitial fibrosis. Distribution of all subtypes of MAPK in renal tissue was no different between IgAN and normal subjects. With the severity of glomerular disease, positive tubules expressed P-ERK or P-JNK increased gradually, especially in PS group, in which expression of P-ERK was 3 fold and P-JNK was 1.6 fold compared to control (P0.05). Expression of JNK protein in tubule was enhanced in PS group. Expression of P-p38 had no change in different groups. P-ERK positive tubules correlated to FN expression.ERK and JNK are strongly expressed and activated in renal tubules in patients with IgAN. It seems that JNK activation is a critical signal to regulate RTEC transdifferentiation, but ERK activation may play an indirect role on this process.

To investigate the role of p38MAPK signaling pathway in interleukin (IL)-1beta induced transdifferentiation and its functional influences in human renal proximal tubular cell line HK-2 cells.Human renal proximal tubular cells, cell line HK-2, were cultured and then co-incubated with IL-1beta (10 ng/ml) for 24 hours. The expression and distribution of cytokeratin and alpha-smooth muscle actin (SMA), markers of transdifferentiation of renal proximal tubular cells, were detected by immunofluorescence staining and confocal microscopy. Western blot technique was used to detect the expression of alpha-SMA 2, 4, 6, 12, 24, and 48 hours after IL-1beta stimulation. The morphology of cells was monitored from the 1st to the 5th day. Expression of alpha-SMA, phosphorylation of p38MAPK was assayed by western blot. Specific p38MAPK inhibitor SB203580 was added into the culture of HK-2 cells, 24 hours later IL-1beta was added for 24 hours Cell-cell adhesion and migration assay were performed. Inverted microscopy was used to examine the morphology of cells after stimulation of IL-1beta for 24 hours. Western blot technique was used to detected total and phosphorylated p38MAPK after stimulation of IL-1beta for 2, 5, 15, 30, 60 and 120 min.The phosphorylation of p38MAPK was increased after treatment of IL-1beta, and reached the level of 1.7 times the basic level 5 - 30 minutes after stimulation (P0.05). Almost no expression of alpha-SMA was shown in the control group. Two hours after IL-1beta stimulation, the expression of alpha-SMA was increased a little followed by an up-regulated expression of alpha-SMA 6 to 48 hours after the stimulation. The expression of alpha-SMA was down-regulated by 40% in the SB203580 group in comparison with that in the control (P0.01) and by 50% in comparison with that in the IL-1beta group (P0.001). The cell number was not significantly different between the IL-1beta group and control group (P0.05). A decreased expression of cytokeratin and disordered distribution of alpha-SMA were shown in the cells 24 hours after stimulation of IL-1beta. The morphology of cells remained unchanged 1 to 5 days after IL-1beta stimulation. The cell-cell adhesion was almost identical in the groups with IL-1beta and/or SB203580 no in comparison with that in the control group (P0.05). The migration ability of HK-2 cells was 2.2 times that in the control group in the IL-1beta group (P0.05) and decreased by 35% in the SB203580 group (P0.01). SB203580 uppercased the IL-1beta-induced expression of alpha-SMA and the enhancement of cell migration ability were suppressed by 51% (P0.05).IL-1beta induces transdifferentiation of renal proximal tubular cells characterized by alpha-SMA expression and enhanced ability of cell migration. These effects are mediated, at least in part, through the activation of p38 MAPK signaling pathway.