Treatment of immunoglobulin G4-related sialadenitis: outcomes of glucocorticoid therapy combined with steroid-sparing agents.

BACKGROUND: Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic disease. Despite its good response to steroid therapy, its treatment protocol is not standardized and the long-term outcome is controversial. The study was conducted to determine the short-term and long-term outcomes of IgG4-RS patients treated with glucocorticoids and steroid-sparing immunosuppressive agents, to analyze secretory function, serological and radiological changes in salivary glands and to assess the usefulness of serum IgG4 level as an indicator of disease activity. METHODS: IgG4-RS patients who were treated for more than 3 months were enrolled. Serological tests, salivary gland function assessment and computed tomography (CT) were performed before treatment and during follow up. The treatment outcomes in the short and the long term were evaluated, and the relationship between serum IgG4 level and salivary gland volume was analyzed. RESULTS: Glucocorticoids were used in all 43 patients and steroid-sparing immunosuppressive agents in 38 patients (88.4%). The follow-up period was 24.6 ± 14.9 months. Clinical remission was achieved in all patients after induction therapy. During short-term observation, salivary gland secretion significantly increased, and the serum IgG4 levels, the volumes and CT values of submandibular and parotid gland decreased significantly (P < 0.001). For long term, relapse occurred in 32.5% patients within 55 months in the regularly treated group, while all seven irregularly treated patients relapsed. However, the relapse-free survival curves were not significantly different between the steroid monotherapy and the combination therapy groups (P = 0.566). Submandibular glands, lacrimal glands, sublingual glands, nasal and paranasal cavity were commonly relapsing organs. In clinically stable patients, a serologically unstable condition occurred in 54.9% patients within 55 months and medication adjustment was performed accordingly. Volume changes in the submandibular and parotid glands were associated with serum IgG4 levels and time of follow up (R2adjusted = 0.905, P < 0.0001 and R2adjusted = 0.9334, P < 0.0001, respectively). CONCLUSIONS: The combination of glucocorticoid and steroid-sparing agents could be effective for treating IgG4-RS, and restoring salivary gland function. Serum IgG4 levels could predict disease activity.

[Effects of Salidroside on Tic Behavior of Tourette Syndrome Model Rats].

OBJECTIVE: To observe the effect of salidroside on tic behavior and in vivo dopamine DA) and serotonin (5-HT) levels in Tourette syndrome (TS) model rats. METHODS: Forty rats were randomly divided into the blank control group, the TS model group, the haloperidol-treated group (0.5 mg/kg x d(-1)), and the salidroside-treated group (50 mg/kg x d(-1)), 10 in each group. TS rat model was induced by imino-dipropio-nitrile (IDPN). Peritoneal injection of haloperidol and salidroside was started from the 4th day of modeling in the haloperidol-treated group and the salidroside-treated group respectively. Normal saline was peritoneally injected to rats in the blank control group and the TS model group respectively. Stereotyped behavior was scored, and changes of DA and 5-HT levels in blood and striatum were measured before modeling, after modeling, and after intervention. RESULTS: Compared with the blank control group, the score of the tic behavior was elevated (P < 0.01) , levels of DA and 5-HT in plasma and striatum were reduced in the model group (P < 0.01, P < 0.05). Compared with the same group after modeling, the tic behavior score decreased and plasma DA levels increased in the two treated groups after intervention (P < 0.01). 5-HT content increased in the salidroside-treated group (P < 0.01). Compared with the model group after intervention, the tic behavior score was significantly reduced (P < 0.01), and DA levels in plasma and striatum were elevated (P < 0.01, P < 0.05) in the salidroside-treated group and the haloperidol-treated group. Compared with the haloperidol-treated group, the tic behavior score increased (P < 0.01), DA levels in plasma and striatum were lowered (P < 0.01, P < 0.05), the 5-HT level increased in plasma and striatum (P < 0.01, P < 0.05) in the salidroside-treated group. CONCLUSIONS: In the salidroside-treated group, the tic behavior was significantly reduced, and DA levels in plasma and striatum were elevated. Its mechanism might be related to regulating activities of dopamine neurons in striatum.

Efficacy and safety of weekly leflunomide for the treatment of early rheumatoid arthritis: a randomized, multi-center study.

AIM: The aim of this study was to determine the efficacy and safety of a weekly dose of leflunomide (50 mg/week) in early rheumatoid arthritis patients with mild or moderate disease activity. METHODS: The patients of early rheumatoid arthritis (ERA) with mild or moderate disease activity were randomly selected for inclusion in this study and were assigned to either the treatment group (leflunomide 50 mg/week, LEF50) or the control group (leflunomide 10 mg/day, LEF10). All patients were treated for 24 weeks. Clinical efficacy was assessed using the disease activity score in 28 joints (DAS28) - erythrocyte sedimentation rate (ESR) and European League Against Rheumatism (EULAR) response. A Chi-squared test, Fisher's exact-test and paired t-tests were used to analyze the data. RESULTS: A total of 244 patients who met the inclusion criteria and received at least one medicine dose were analyzed. At the baseline, the DAS28 (ESR) of the ERA patients were 4.41 ± 0.69 in LEF 50 group and 4.52 ± 0.64 in LEF 10 group, respectively. At week 24, the DAS28 (ESR) in two groups ( 2.94 ± 1.10 and 3.02 ± 1.14 ) were significant decreased compare with the baseline, respectively (P<0.01). There was no significant difference in DAS28 (ESR) between the LEF50 and LEF10 groups at week 24. (P > 0.05). At weeks 8, 12 and 24, the EULAR response (good responses + moderate responses) were 47.6%, 58.7% and 59.5%, in the LEF50 group and 43.2%, 49.1% and 53.4% in the LEF10 group, respectively. There was no significant different of EULAR response rates in the two groups at week 8, 12, and 24, respectively (P>0.05). There was no serious adverse events during the study. CONCLUSION: A weekly dose of 50 mg leflunomide showed similar benefits to a daily dose of 10 mg leflunomide for the treatment of mild-to-moderate early rheumatoid arthritis.

AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway.

To investigate apoptosis mechanisms in lymphocytes induced by aluminum trichloride (AlCl3) through the mitochondria-caspase dependent pathway, the spleen lymphocytes of rats were cultured with RPMI-1640 medium and exposed to AlCl3·6H2O in the final concentrations of 0 (control group, CG), 0.3 (low-dose group, LG), 0.6 (mid-dose group, MG), and 1.2 (high-dose group, HG) mmol·L(-1) for 24 h, respectively. Mitochondrial transmembrane potential (ΔΨm), cytochrome C (Cyt C) protein expression in cytoplasm, Caspase-3 and Caspase-9 activity, Bcl-2, Bax, Caspase-3 and Caspase-9 mRNA expressions, DNA ladder and lymphocytes apoptosis index were detected. The results showed that Cyt C protein expression in cytoplasm, Caspase-3 and Caspase-9 activity, Bcl-2, Bax, Caspase-3 and Caspase-9 mRNA expressions, the ratio of Bcl-2 and Bax mRNA expression, lymphocytes apoptosis index increased, while ΔΨm decreased in the AlCl3-treated groups compared with those in CG. The results indicate that AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway.

A survey of anxiety and depression symptoms among primary-care physicians in China.

OBJECTIVE: Anxiety and depression disorder are the most prevalent mental health problems. However, few studies are available pertaining to these problems among Chinese doctors, especially the assessment of the anxiety and depression symptoms among primary-care providers. The aim of this study was to assess the anxiety and depression symptoms among Chinese primary-care physicians and their associated factors. METHODS: A cross-sectional study was conducted among 451 primary-care physicians in Shanghai China (effective response rate was 79.8%). There were 177 male physicians and 274 female physicians with average age of 37.8 (SD +/- 11.1) years. Questionnaire pertaining to depression disorder was indicated by the Zung Self-Rating Depression Scale (SDS) and anxiety disorder was indicated by the Zung Self-Rating Anxiety Scale (SAS). RESULTS: The average SAS and SDS standard scores of the primary-care physicians were 41.1 +/- 11.5 and 46.5 +/- 11.8 respectively. Both of the scale scores were higher than those of Chinese national norms (P both < 0.001). SDS standard score > or = 53 and SAS standard score > or = 50 were regarded as screening-positive criteria. SAS and SDS screening positive rates of primary-care physicians were 18.0% and 31.7% respectively. In addition, married/cohabited and divorced/widowed physicians aged over 30 years with educational background of junior college had higher risks of anxiety and depression disorders. CONCLUSIONS: Chinese primary-care physicians were at considerably high risk of anxiety and depression disorders, which was worthy of attention during healthcare system reform in China.

Epidemiology of eight common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing.

OBJECTIVE: To investigate the prevalence of eight common rheumatic diseases in a large Chinese population. METHODS: A population-based epidemiological investigation of the prevalence of eight common rheumatic diseases in a suburb of Beijing was conducted in 14 642 individuals. A community-based survey was carried out using a screening questionnaire. Positive responders were included in a clinical and laboratory examination. Diagnosis was based on the criteria of ACR or those used widely in literature. RESULTS: A total of 10 556 inhabitants were interviewed. Forty-three cases of RA were identified with an age-adjusted prevalence of 0.28% (95% CI 0.19%, 0.41%). Gout was diagnosed with a crude prevalence of 0.09% (95% CI 0.05%, 0.17%). Psoriasis was reported in 28 individuals with a prevalence of 0.27% (95% CI 0.18%, 0.38%). This included two cases diagnosed with PsA, resulting in a prevalence of 7.14% (95% CI 0.88%, 23.5%) in psoriasis patients and 0.02% (95% CI 0%, 0.07%) in the general population. Three individuals were identified with SLE, with a prevalence of 0.03% (95% CI 0%, 0.06%). One individual was identified with SSc and the calculated prevalence was 0.01% (95% CI 0%, 0.05%). One case of Behçet's disease was identified, giving a prevalence of 0.01% (95% CI 0%, 0.05%). CONCLUSION: This large-scale epidemiological survey provides an estimate of the burden of rheumatic diseases in China.

[The clinical significance of D-dimer in systemic lupus erythematosus].

OBJECTIVE: To investigate the clinical significance of D-dimer in systemic lupus erythematosus (SLE). METHODS: The study group comprised 261 SLE patients who were admitted in ward from 2005 to 2008 in Peking University People's Hospital. Collect the clinical data to investigate the clinical significance of D-dimer. RESULTS: (1) The D-dimer levels of 56 patients were increased due to coexist reduced renal function, infections, disseminated intravascular coagulation (DIC), liver disorders, pregnancy and injury. With the exception of above patients, 142 (69.3%) patients were increased in total 205 patients. (2) The level of D-dimer was positively correlated with SLE disease activity index (SLEDAI) score (r = 0.598, P = 0.000), and was associated with anti-dsDNA antibody, ESR, C-reactive protein (CRP) and complement C(3) and C(4). (3) D-dimer level was associated with important organ involvement. (4) All patients with thrombosis had increased D-dimer, but patients without thrombosis had normal or increased D-dimer levels. CONCLUSION: The level of D-dimer elevates in patients with active disease or important organ involvement, it can not identify thrombosis. All patients with thrombosis had increased D-dimer levels.

Assessing heavy-metal contamination and sources by GIS-based approach and multivariate analysis of urban-rural topsoils in Wuhan, central China.

Nine potentially harmful heavy metals (Cd, Co, Cr, Cu, Hg, Mn, Pb, Ni, and Zn) were measured in 477 topsoil samples collected from urban-rural areas in the city of Wuhan in order to identify their concentrations and possible sources, and characterize their spatial variability for risk assessment. Results showed that in most rural areas heavy-metal concentrations in soil were similar to their natural background values, but Cd, Cu, Hg, Pb, and Zn concentrations were relatively higher in densely populated districts and around industrial facilities. Multivariate analyses (correlation matrix, principal component analysis, and cluster analysis) indicated that Cd, Cu, Hg, Pb, and Zn were mainly derived from anthropogenic inputs, and Co, Cr, and Mn were controlled by natural source, whereas Ni appeared to be affected by both anthropogenic and natural sources. The result of risk assessment indicated that nearly 48% of the study area suffered from moderate to severe contamination.

[Possible mechanisms of peripheral elevated CD8+ IL-17+ T cells in rheumatoid arthritis].

OBJECTIVE: To identify interleukin-17 (IL-17 )-producing CD8 positive T cells from patients with rheumatoid arthritis (RA), and investigate its cytokines as well as their correlations. METHODS: Peripheral blood got from 39 RA patients and 40 healthy donors. Flow cytometry was used to analyze the subsets of T cells in peripheral blood from these 39 RA patients and 27 healthy donors. 11-17, IL-6, and IL-23 levels in sera of all these people were tested by ELISA. RESULTS: The median of CD8 IL-17+ T cells from RA patients was 2.7% (95% confidence internal was 1.55%-3.74%); the median of these cells from healthy controls was 1.61% (95% confidence internal was 1.25%-2.61%). CD8+ IL-17+ T cells elevated significantly in RA(P < 0.05). As the production of CD8+ IL-17+ T cells, the IL-17 levels in sera of RA patients and healthy controls were (429 +/- 502) ng/L and (13 +/- 30) ng/L respectively. The IL-17 level in RA is higher than that in healthy people (P < 0.01). Meanwhile, to constitute CD8+ IL-17+ T cell polarizing condition, IL-23 and IL-6 in sera of RA were (157.83 +/- 27.07) ng/L and (32.67 +/- 34.50) x ng/L individually. These two cytokines in healthy controls were (21.97 +/- 3.52) ng/L and (1.82 +/- 1.51) ng/L severally. IL-6 and IL-23 increased clearly in peripheral blood of RA patients as compared with healthy donors (P < 0.01). CONCLUSIONS: This study suggested that elevated CD8+ IL-17+ T cells which involved in IL-17 secretion may depend on increased IL-6 and IL-23 in peripheral blood of rheumatoid arthritis.

[Studies on the physiological response of Phytolacca americana to manganese toxicity by FTIR spectroscopy].

A technique based on Fourier transform infrared (FTIR) spectrometry was used to detect the physiological changes in chemical composition of Phytolacca americana under a wide range of Mn2+ treatments (0, 0.125, 0.25, 0.5 and 1 g x kg(-1)). Using the roots, stems and leaves of phytolacca americana, absorption bands corresponding to carbohydrates, ester and proteins varied differently. The absorption band heights at 3 000 and 2 916 cm(-1) of stem tissues rose firstly and then decreased, indicating the exudation and transporting situation of organic substances which served as organic osmotic contents to enhance manganese tolerance under low treatments; Meanwhile, the band heights at 2 922 cm(-1) (roots) and 1 606 cm(-1) (leaves) which have different tendency in accordance with Mn treatments showed that the capability to chelate Mn decreased under higher manganese concentration. In addition, the changes of the bands at 1 732 and 1 026 cm(-1) (roots), 1 028 cm(-1) (stems), 1 052 and 967 cm(-1) (leaves) differed from each other, suggesting that under the conditions of severe Mn stress the ex-oxidation of membrane lipid increased; Otherwise, the band heights at 1 375 cm(-1) increased firstly and then decreased, representing that the cell wall improved Mn resistance by increasing cation-exchange capacity (CEC). The result also implied that it is practical to apply FTIR to the research comparing the chemical differences of phytoaccumulators under metal treatments.

[Therapeutic effect and impact on cytokine production by methotrexate in rheumatoid arthritis].

OBJECTIVE: To examine the clinical benefit and impact on cytokine production by methotrexate in rheumatoid arthritis. METHODS: Thirty patients with RA were treated with oral methotrexate (mean, 15 mg per week) as monotherapy for 24 weeks. Clinical assessment using the American College of Rheumatology (ACR) criteria for improvement was performed at baseline and at the end of 2, 4, 8, 12 and 24 weeks. The pro-inflammation cytokine TNF-alpha, INF-gamma,IL-1beta, IL-6 and anti-inflammation cytokine IL-10 were measured in RA sera at baseline and after 24 weeks of therapy. RESULTS: There was remarkable improvement in disease activity following the MTX treatment. At the end of 24 weeks, the percent age of ACR20 was 70% (21/30), ACR50 30% (9/30) and ACR70 10% (3/30). The levels of IL-6 (46.83+/-35.81 vs. 20.92+/-17.98, P=0.001), TNF-alpha (162.52+/-107.63 vs. 18.32+/-14.36, P=0.026) and INF-gamma (67.79+/-43.76 vs. 35.78+/-27.51, P=0.004) were significantly higher than those of the health control at baseline, respectively. The levels of TNF-alpha (123.36+/-89.61,P=0.018), INF-gamma (41.53+/-13.49, P=0.015), IL-1beta (7.47+/-7.33, P=0.026), IL-6 (26.01+/-25.64, P=0.025) were significantly decreased after treatment with methotrexate. In contrast, IL-10 was remarkably increased (71.76+/-41.01, P=0.02). CONCLUSION: Methotrexate is effective in patients with rheumatoid arthritis. It can suppress the symptoms and joint damage. In addition, methotrexate treatment decreases the levels of pro-inflammatory cytokine, and increases the level of anti-inflammatory cytokine.

[Glucose metabolism status and angiographic features of coronary artery in patients undergoing their first coronary angiography: study of 553 cases].

OBJECTIVE: To investigate the correlation between glucose metabolism status and coronary artery lesion in the patients undergoing their first coronary angiography (CAG). METHODS: Oral glucose tolerance test (OGTT) and CAG were performed in 553 patients with suspected or confirmed coronary artery disease (CAD), aged 60.1 +/- 9.7. The anthroposomatologic parameters, blood pressure, HbA1c, and lipid profile of these patients were collected. Their glucose metabolism status was assessed based on the WHO diagnostic criteria of diabetes mellitus 1999 and American Heart Association's grading standards for evaluating coronary artery stenosis and Gensini score were applied to analyze the coronary artery lesion. According to the CAG results the patients were divided into CAD group and non-CAD group and then the glucose metabolic characteristics in both groups were analyzed by comparison based on the glycometabolic status. The patients were also grouped into diabetic and non-diabetic groups and the coronary artery angiographic features in both groups were compared. RESULTS: Among the 533 patients 277 (50.1%) had normal OGTT, 127 (23.0%) were diagnosed as with impaired glucose regulation, 61 (11%) were newly diagnosed as with type 2 diabetes mellitus, and the other 88 patients (15.9%) were already known diabetics. The prevalence of abnormal glycometabolism in the CAD group was 56.4%, significantly higher than that in the non-CAD group (34.5%, P < 0.05). The prevalence of multiple branches involvement in the diabetic group was 63.8%, significantly higher than that of the non-diabetic group (44.1%, P < 0.05), and the Gensini score in the diabetic group was 15 (30.5), significantly higher than that of the [20 (27), P < 0.05]. CONCLUSION: Abnormal glycometabolism is common in the population undergoing coronary angiography. Both the prevalence of multiple branches involvement and the degree of stenosis of coronary in the diabetics are higher than that in those without diabetes.

[Analysis on the trend of severe acute respiratory syndrome epidemic in Inner Mongolian Autonomous Region].

OBJECTIVE: To analyse the severe acute respiratory syndrome (SARS) epidemics in Inner Mongolian Autonomous Region and to provide scientific basis for prevention and control strategies against it. METHODS: Data from legal communicable diseases surveillance reporting system was analyzed epidemiologically. RESULTS: The first SARS case was reported in Inner Mongolian Autonomous Region on March 27, 2003. Up to May 20, there were 446 cumulative SARS cases in the whole region (with 287 confirmed cases and 159 suspected cases) and 61 cumulative recovered cases had been discharged from the hospitals (56 confirmed cases and 5 suspected cases). Another 131 cases were excluded the original diagnoses of SARS including 10 confirmed cases and 121 suspected cases. 25 confirmed cases died with a mortality rate of 8.7%. Cumulatively, the number of reported cases were distributed in 30 counties in 9 prefectures. Statistical analysis on time sequence of the occurrence of cases showed that majority (67.7% of the total) of the cases concentrated in between April 13 and April 29. The number of cases had started to decrease since April 24 with an average of 5.3 cases per day between May 3 and May 8 and an average of 0.3 cases per day between May 9 and today. CONCLUSIONS: SARS epidemics in our region could be divided into three phases. The first phase fell in between March 18 and April 15 with the first case being imported, the number of cases rose sharply, covering 14 counties in 6 prefectures, having a feature of family clustering. The second phase was from April 16 to April 28, with the appearance of secondary infection, having sharp rise of the cases and spreading to 24 counties in 10 prefectures. One of the major features was that hospitals had become the important sources of secondary infection. Finally, the third phase was between April 29 and May 20, with small wave crests of cases, spreading to 38 counties in 10 prefectures with a high proportion of cases with no history of direct contact with diagnosed SARS patients. Thus, no obvious transmission chain was noticed at this phase.

Re-expression of p16 gene in the myeloma cell line U266 induced by synergy of sodium butyrate and 5-Aza-2'-deoxycytidine.

OBJECTIVE: To understand the synergic effect of histone deacetylase inhibitor sodium butyrate (SB) and demethylating agent 5-Aza-2'- deoxycytidine (5-Aza-CdR) on cell growth and to explore the possibility of re-expression of the hypermethylated and silenced p16 gene in the myeloma cell line U266. METHODS: U266 cells were cultured in RPMI 1640 in the presence of varied doses of SB and 5-Aza-CdR, and the growth curve was obtained by trypan-blue exclusion assay and cell count. The cell cycle was analyzed by flow cytometry and the expression level of mRNA and protein of p16 gene were detected by reverse transcriptase-PCR and Western blotting, respectively. RESULTS: The cell growth was arrested by treatment with 5-Aza-CdR alone or SB alone. Increased inhibition effect was shown in synergic treatment of SB and 5-Aza-CdR. The G(1) phase of cell cycle was arrested by 5-Aza-CdR combined with SB, which, however, did not occur when SB or 5-Aza-CdR was used alone. 5-Aza-CdR alone induced the expression of p16 gene in a concentration-dependent manner, whereas SB alone only induced its low-level expression. The expression level of both mRNA and protein of p16 gene was increased significantly by synergic application of SB and 5-Aza-CdR. CONCLUSION: Hypermethylated and silenced p16 gene in U266 cell line can be markedly reactivated by synergic treatment with demethylating agent 5-Aza-CdR and histone deacetylase inhibitor SB, and the cell growth can be inhibited and cell cycle arrested at G(1) phase.