B cell subsets in adult-onset Still's disease: potential candidates for disease pathogenesis and immunophenotyping.

BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder of unknown etiology. B cells are critical participants in different rheumatic diseases, and their roles in AOSD are rarely investigated. This study aimed to unveil the B cell subset features in AOSD and provide evidence for B cell-based diagnosis and targeted therapies of AOSD. METHODS: B cell subsets in the peripheral blood of AOSD patients and healthy controls (HCs) were detected by flow cytometry. Firstly, the frequencies of B cell subsets were compared. Then, the correlation analysis was performed to explore the correlation between B cell subsets and clinical manifestations in AOSD. Finally, unbiased hierarchical clustering was performed to divide AOSD patients into three groups with different B cell subset features, and the clinical characteristics of the three groups were compared. RESULTS: The frequencies of B cell subsets were altered in AOSD patients. Disease-promoting subsets (such as naïve B cells, double negative B cells (DN B cells), and plasmablasts) increased, and potential regulatory subsets (such as unswitched memory B cells (UM B cells) and CD24hiCD27+ B cells (B10 cells)) decreased in the peripheral blood of AOSD patients. In addition, the altered B cell subsets in AOSD correlated with the clinical and immunological features, such as immune cells, coagulation features, and liver enzymes. Intriguingly, AOSD patients could be divided into three groups with distinct B cell immunophenotyping: group 1 (naïve B cells-dominant), group 2 (CD27+ memory B cells-dominant), and group 3 (precursors of autoantibody-producing plasma cells-dominant). Moreover, these three group patients demonstrated differential manifestations, including immune cells, liver or myocardial enzymes, coagulation features, and systemic score. CONCLUSIONS: B cell subsets are significantly altered in AOSD patients, potentially contributing to the disease pathogenesis. These findings would inspire B cell-based diagnosis and targeted therapies for this refractory disease.

Decreased perforin-producing B cells correlate with systemic lupus erythematosus.

OBJECTIVES: It has been proved that B cells play indispensable roles in immunity via producing cytokines and secreting antibodies. Aberrant B cells are considered as the major participants in the pathogenesis of systemic lupus erythematosus (SLE). Recently, perforin (PFP)-producing B cell has been identified, serving as a new type of potential anti-tumour effector cells. However, the roles and characteristics of the PFP-producing B cells in SLE remain unclear. METHODS: The frequencies of PFP-producing B cells in peripheral blood of heathy controls (HC) and SLE patients were detected by flow cytometry, and their correlation with the patient clinical and immunological features were analysed. The capacities of these cells in producing PFP were also compared between HC and SLE by RT-qPCR and ELISpot analyses. RESULTS: In this study, we demonstrated that B cells could produce PFP and was further enhanced upon anti-BCR and IL-21 stimulation. In patients with SLE, the frequencies of these PFP-producing B cells were decreased and negatively correlated with the clinical characteristics. Further analysis revealed that SLE patients with vasculitis and pleurisy showed even lower frequencies of PFP-producing B cells. CONCLUSIONS: These findings revealed that B cells could produce PFP, and a decrease in these cells was associated with SLE pathogenesis.

Tonsillar Microbiome-Derived Lantibiotics Induce Structural Changes of IL-6 and IL-21 Receptors and Modulate Host Immunity.

Emerging evidence emphasizes the functional impacts of host microbiome on the etiopathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). However, there are limited mechanistic insights into the contribution of microbial biomolecules especially microbial peptides toward modulating immune homeostasis. Here, by mining the metagenomics data of tonsillar microbiome, a deficiency of the encoding genes of lantibiotic peptides salivaricins in RA patients is identified, which shows strong correlation with circulating immune cells. Evidence is provided that the salivaricins exert immunomodulatory effects in inhibiting T follicular helper (Tfh) cell differentiation and interleukin-21 (IL-21) production. Mechanically, salivaricins directly bind to and induce conformational changes of IL-6 and IL-21 receptors, thereby inhibiting the bindings of IL-6 and IL-21 to their receptors and suppressing the downstream signaling pathway. Finally, salivaricin administration exerts both prophylactic and therapeutic effects against experimental arthritis in a murine model of RA. Together, these results provide a mechanism link of microbial peptides-mediated immunomodulation.

Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial.

Rheumatoid arthritis (RA) is an aggressive autoimmune arthritis, and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects. Low-dose interleukin-2 (Ld-IL2) is potentially a therapeutic approach to further improve the disease. This randomized, double-blind, placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA. Patients were randomly assigned (1:1) to receive Ld-IL2, defined as a dose of 1 million IU, or placebo in a 12-week trial with a 12-week follow-up. Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks (a total of 7 doses), followed by a 2-week break. All patients received a stable dose of methotrexate (MTX). The primary outcomes were the proportion of patients achieving the ACR20, DAS28-ESR <2.6, and the change from baseline in CDAI or SDAI at week 24. Secondary endpoints included other clinical responses and safety. The primary outcomes were achieved in the per-protocol population. The improvements from baseline in CDAI and SDAI were significantly greater across time points for the Ld-IL2 + MTX group (n = 17) than for the placebo+MTX group (n = 23) (P = 0.018 and P = 0.015, respectively). More patients achieved ACR20 response in the Ld-IL2 + MTX group than those in the placebo+MTX group at week 12 (70.6% vs 43.5%) and at week 24 (76.5% vs 56.5%) (P = 0.014). In addition, low Treg and high IL-21 were associated with good responses to Ld-IL2. Ld-IL-2 treatment was well-tolerated in this study. These results suggested that Ld-IL2 was effective and safe in RA. ClinicalTrials.gov number: NCT02467504.

Clinical assessment of cardiac impairment favored by two-dimensional speckle tracking echocardiology in patients with systemic sclerosis.

BACKGROUND: Cardiac involvement is a major cause of death in SSc, while early detection remains a challenge. OBJECTIVES: The purpose of this study was to investigate the prevalence and clinical implications of cardiac impairment in SSc. METHODS: Ninety-five consecutive SSc patients [55.6 (13.8) years old, 5.3 (8.1) years from diagnosis] were included in the study. Patients with heart diseases onset prior to SSc were excluded. All patients underwent two-dimensional speckle-tracking echocardiology (2D-STE) with measuring left and right ventricular global longitudinal strain (GLS/RGLS). Clinical manifestation, laboratory evaluation (CRP, cTnI, antibodies, etc.) and ECG were collected at the same time. Comparisons between the SSc subgroups (lcSSc and dcSSc) were performed using Student's t-test, Mann-Whitney U or Fisher's exact test. Binary logistic regression was applied to determine the independent effects of variables in cardiac impairment. RESULTS: Early left and right ventricular impairment measured by GLS and RGLS were detected in 22.1% and 24.2% of the SSc patients, respectively. In comparison, only 2.1% showed reduced left ventricular ejection fraction (LVEF). Impaired GLS was mainly observed in the basal and medial segments of anterior, lateral and posterior left ventricle walls, and more profound in dcSSc. Elevated CRP (OR 3.561 95% CI: 1.071, 11.839, P <0.05) was associated with reduced GLS/RGLS. The adoption of GLS/RGLS enhanced the efficacy of routine screening for cardiac impairment that 52.6% of patients showed potential cardiac impairment. CONCLUSIONS: Cardiac impairment is a common manifestation in SSc. Increasing awareness of early cardiac impairment is warranted with elevated CRP and dcSSc.

Salivary gland ultrasonography in primary Sjögren's syndrome from diagnosis to clinical stratification: a multicentre study.

BACKGROUND: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjögren's syndrome (pSS) using the novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system in a large-scale multicentre study. METHODS: SGUS was conducted for 246 pSS patients, 140 control subjects with conditions other than SS and 27 healthy control subjects. The echostructure features from the parotid and submandibular glands on both sides were graded using the novel OMERACT scoring system. Receiver operating characteristic curves were used to describe the diagnostic accuracy of the scoring system for pSS. The associations between the SGUS and disease characteristics were analysed to evaluate the clinical value of SGUS for pSS. RESULTS: The US scores in the pSS group were significantly higher than those in the non-pSS group (p < 0.001). The level of diagnostic accuracy was comparable with the scores of all four glands (AUC=0.908) when only the parotid and submandibular glands on either side were scored (AUC=0.910, 0.904, respectively). The optimal cut-off value for the left (right) parotid gland and the left (right) submandibular gland was 4, with maximal sensitivity (75.6% and 77.2%, respectively) and specificity (91.6% and 92.2%, respectively). The pSS patients with positive SGUS results presented a longer disease duration, parotid enlargement, dental loss and higher levels of serological markers, such as anti-SSA, anti-SSB, positive RF, IgG and γ-globulin%. CONCLUSIONS: SGUS with the OMERACT scoring system yields high sensitivity and specificity, demonstrating high diagnostic feasibility for pSS. The SGUS may have implications for deciding disease severity and treatment efficacy.

Impaired granzyme B-producing regulatory B cells in systemic lupus erythematosus.

Granzyme B (GrB)-producing B cells are proposed to be a kind of regulatory B cells (Bregs) and have been revealed to be implicated in the pathogenesis of autoimmune diseases. Nevertheless, their role in SLE remains elusive. In this study, the frequencies of GrB-producing Bregs in peripheral blood of heathy control (HC) and systemic lupus erythematosus (SLE) were evaluated by flow cytometry, and their correlation with SLE patient clinical and immunological features were analyzed. The expression of GrB in HC and SLE B cells were also further detected by RT-qPCR analysis and ELISpot. The function of GrB-producing Bregs in HC and SLE patients was further investigated by in vitro CD4+ effector T cells-B cells co-culture assays with GrB blockade. We found that GrB-producing Bregs were significantly decreased in SLE patients and correlated with the clinical and immunological features. Moreover, these cells were functionally impaired under SLE circumstance. The negative correlation between GrB-producing Bregs and CD4+ T cells observed in healthy individuals disappeared in SLE patients. In vitro cell co-culture assay further showed that GrB-producing Bregs from SLE patients failed to suppress the Th1, Th2 and Th17 cell inflammatory responses, partially due to the dampened capacity of down-regulating TCR zeta and inducing T cell apoptosis. Taken together, these results revealed the disturbance of GrB-producing Bregs in SLE that might contribute to the disease initiation and progression.

Sonoelastography of salivary glands for diagnosis and clinical evaluation in primary Sjögren's syndrome.

OBJECTIVES: To explore the performance of sonoelastography (SE) in diagnosis and clinical evaluation of primary Sjögren's syndrome (pSS). METHODS: SE examination of major salivary glands was conducted for 79 pSS patients, 39 disease controls and 15 healthy subjects. Elastographic images were determined with a qualitative 4-point scoring method. Receiver operating characteristic (ROC) curve was employed to evaluate the performance of the elasticity scoring method and the best cut-off value was determined. The associations between elasticity scores and disease characteristics were analysed to evaluate the clinical value of SE for pSS. RESULTS: Elasticity scores of parotid and submandibular glands in pSS group were significantly higher than those in the non-pSS group (p<0.001). The sum of the scores of all four glands provided the largest AUC-ROC (0.916, 95% CI 0.87-0.962), compared with that of bilateral parotid glands (0.857, 95% CI 0.794-0.919) and that of bilateral submandibular glands (0.783, 95% CI 0.704-0.863). The optimal cut-off value was 9 for combined evaluation of all four glands (81% sensitivity and 87% specificity, respectively). The elasticity scores of parotid glands in patients with disease duration >10 years experienced significant difference as compared to patients with disease duration ≤5 years and 5-10 years respectively (p=0.007, 0.009, respectively), whereas it presented no variations between the disease duration ≤5 years and 5-10 years (p=0.952). CONCLUSIONS: Sonoelastography, performed simultaneously with ultrasonography, is an additional tool for the assessment of the salivary glands in patients with pSS. The elasticity is closely associated with disease duration.

The performance of the diagnostic scoring system or criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis for adult-onset Still's disease. A multicentre case-control study in China.

OBJECTIVES: To evaluate the performance of the diagnostic scoring system/criteria for macrophage activation syndrome (MAS) used in systemic juvenile idiopathic arthritis (sJIA) for adult-onset Still's disease (AOSD). METHODS: This retrospective case-control study included AOSD patients with and without MAS from six hospitals in China. The cut-off values that best discriminated MAS from active AOSD were determined by receiver operating characteristic (ROC) curve analysis. The performance of the present diagnostic scoring system/criteria for sJIA-MAS was evaluated in AOSD-associated MAS. The optimal critical value of the ROC curve replaces the relevant indicators of the existing scoring system and different models were tested for sensitivity/specificity. RESULTS: A total of 56 AOSD-associated MAS patients (AOSD-MAS) and 112 AOSD patients without MAS matched with age and sex treated at six centres between 2007 and 2017 were enrolled. The 2016 MAS in sJIA classification criteria had an overall sensitivity of 100.0% and specificity of 80.4% for classifying AOSD-MAS. Excluding hypertriglyceridemia and substituting some other criteria with newly obtained cut-off values could increase specificity. An MS score ≥-2.1 yielded a sensitivity of 95.2% and a specificity of 76.6% in classifying AOSD-MAS. ROC curve analysis revealed that a score of -1.74 could best discriminate AOSD-MAS from AOSD without MAS. An MS score ≥-1.74 yielded a sensitivity of 93.5% and a specificity of 92.6% in diagnosing AOSD-MAS (AUC=0.96, 95%CI: 0.93-0.99, p<0.0001). CONCLUSIONS: The diagnostic tool for MAS in sJIA with modification appears to apply to AOSD-MAS.

Elevated Serum Human Epididymis Protein 4 Is Associated With Disease Activity and Systemic Involvements in Primary Sjögren's Syndrome.

Background: We aimed to investigate the clinical utility of human epididymis protein 4, a tumor biomarker being widely utilized in clinical practice in the diagnosis of ovarian cancer, in primary Sjögren's Syndrome (pSS). Methods: A total of 109 pSS patients and 113 healthy controls (HCs) were included in the study. HE4 were determined by Roche Cobas E601 electrochemical luminescence analyzer. Clinical and laboratory findings were reviewed, and the relationships between HE4 and clinical parameters were determined by Spearman's correlation test. The European league against rheumatism Sjögren's syndrome disease activity index (ESSDAI) was utilized to evaluate disease activity. Findings: The levels of HE4 were significantly elevated in patients with pSS compared to HCs (103.65 pmol/L vs. 46.52 pmol/L, p<0.001). The levels of HE4 were positively correlated with ESSDAI scores (r=0.462, p<0.001). Significant positive correlations between the levels of HE4 with pulmonary involvements (r=0.442, p<0.001) and renal involvements (r=0.320, p=0.001) were observed. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.90 pmol/L and 128.05 pmol/L for distinguishing patients with pulmonary and renal involvements, with the areas under the ROC curve (AUCs) of 0.778 (95%CI 0.685-0.870, p<0.001) and 0.768 (95%CI 0.646-0.891, p=0.001), respectively. Among patients with pulmonary involvement, the levels of HE4 were positively correlated with the semiquantitative HRCT grade (r=0.417, p=0.016), and negatively correlated with the percentage of forced vital capacity (FVC) (r= -0.460, p=0.047) and diffusing capacity of the lung for carbon monoxide (DLco) (r= -0.623, p=0.004). For patients with renal involvement, HE4 was positively correlated with creatinine (r=0.588, p=0.021) and negatively correlated with estimated glomerular filtration rate (r= -0.599, p=0.030). Conclusions: Our findings demonstrated a novel role of HE4 in clinical stratification of pSS, suggesting that introducing HE4 to the current pSS test panel may provide additional diagnostic value, particularly in evaluating disease activity and pulmonary/renal involvements.

Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune disease characterized by altered balance of activity between effector and regulatory CD4(+) T cells. The homeostasis of CD4(+) T cell subsets is regulated by interleukin (IL)-2, and reduced production of IL-2 by T cells is observed in individuals with SLE. Here we report that treatment with low-dose recombinant human IL-2 selectively modulated the abundance of regulatory T (Treg) cells, follicular helper T (TFH) cells and IL-17-producing helper T (TH17) cells, but not TH1 or TH2 cells, accompanied by marked reductions of disease activity in patients with SLE.

[Clinical and laboratory features of psoriatic arthritis which antedates psoriasis].

OBJECTIVE: To analyze the clinical and laboratory features of psoriatic arthritis (PsA) which antedates psoriasis. METHODS: The clinical and laboratory data including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), immunoglobulins, antibodies of 113 patients with PsA were analyzed retrospectively and compared by order of the occurrence of arthritis. RESULTS: The occurrence of psoriatic arthritis which antedates psoriasis was 22.1% in the study. The onset of arthritis was 2 months to 25 years earlier than psoriasis. Arthritis of distal interphalangeal (DIP) joints was frequently involved in this group and arthritis of hip joints was rare. Positive HLA-B27 and higher level of platelet (PLT), ESR, CRP, and IgA were common in patients with psoriatic arthritis which antedates psoriasis. CONCLUSION: Arthritis of DIP joints and elevated inflammatory markers are frequently involved in patients with psoriatic arthritis which antedates psoriasis, and somewhat they are associated with disease activity.

Magnetic resonance imaging in early rheumatoid arthritis: a multicenter, prospective study.

To identify the magnetic resonance imaging (MRI) features of hands and wrists in early rheumatoid arthritis (RA). A total of 129 early arthritis patients (≤1 year) were enrolled in the study. At presentation, MRI of the hands was performed, with clinical and laboratory analyses. After a 1-year follow-up, clinical diagnosis of early RA or non-RA was confirmed by two rheumatologists. The characteristics of MRI variables at baseline in RA patients not fulfilling ACR 1987 criteria [RA-87(-)] were compared with those fulfilling ACR1987 criteria [RA-87(+)] and non-RA. In the 129 early arthritis patients, 90 were diagnosed with RA in a 1-year follow-up. There were 47.8 % (43/90) of the RA patients not fulfilling ACR 1987 criteria [RA-87(-)]. The scores of synovitis in RA-87(-) patients were similar with those in RA-87(+) [Synovitis score, 14.0 (IQR, 4.0-25.0) vs. 14.0 (IQR, 10.0-25.0), p > 0.05]. Compared with those in non-RA, RA-87(-) patients had higher synovitis scores and occurrence of synovitis in proximal interphalangeal (PIP) joints [synovitis score, 14.0 (IQR, 4.0-25.0) vs. 6.0 (IQR, 2.0-14.5), p = 0.046; occurrence of PIP synovitis: 53.5 vs. 27.3 %, p = 0.02]. There was no significant difference of bone marrow edema, bone erosion, and tenosynovitis between RA-87(-) and non-RA. Synovitis in PIP joints was independent predictor for RA-87(-) [OR, 3.1 (95 %CI 1.2-8.1)]. High synovitis scores and synovitis in PIP joints on MRI were important in early RA, especially those not fulfilling ACR 1987 criteria.

[Clinical characteristics and treatment outcomes of microscopic polyangiitis combined with autoimmune hemolytic anemia].

OBJECTIVE: To investigate the clinical characteristics, laboratory features, outcome and prognosis of microscopic polyangiitis (MPA) patients with autoimmune hemolytic anemia (AIHA). METHODS: In this study, 63 cases diagnosed as MPA from October 2006 to November 2013 in Peking University People's Hospital were reviewed. The clinical characteristics, outcome and prognosis of MPA patients with AIHA were retrospectively analyzed. RESULTS: There were 12.7% (8/63) MPA patients with AIHA. The patients with AIHA had higher prevalence of fever, fatigue, hematuresis, albuminuria and new-onset hypertension, compared with non-AIHA group(87.5% vs.29.1%;100% vs. 49.1%; 100% vs. 60%; 75% vs. 20%, all P<0.05). In patients with AIHA, there were significantly lower levels of red blood cell(RBC), hemoglobin(Hb), alanine albumin(Alb) and complement C3[(2.3±0.5)×10(12)/L vs.(3.0±0.7)×10(12)/L;(66.2±13.1) g/L vs.(90.0±20.3) g/L; (26.1±4.4) g/L vs. (33.5±6.4) g/L; (0.7±0.2) g/L vs.(0.9±0.3) g/L,all P<0.05]. However, the levels of erythrocyte sedimentation rate (ESR), IgG and Birmingham Vasculitis Activity Score (BVAS) were higher, compared with those in the patients without AIHA [(102.1±25.7) mm/1 h vs.(76.5±31.1) mm/1 h; (20.9±6.1) g/L vs. (14.5±6.0) g/L; ( 23.7±5.7) vs.(17.3±4.1), all P<0.05]. The study suggested that there were more severe multi-system damage in the patients with AIHA than in those without AIHA. In the MPA patients with AIHA, six cases received treatment of methylprednisolone combined with immunosuppressant, and two received treatment of methylprednisolone only. Among the eight cases, three were recovered from anemia and four improved. One died of severe lung infection. After 4 years follow-up,in the seven MPA patients with AIHA, three received remission, two died,and two suffered from anemia and abnormal renal function. CONCLUSION: MPA with AIHA is more complicated by multi-system damage and not rare in clinical settings. Glucocorticoid combined with immunosuppressant is beneficial to induce remission for MPA patients with AIHA.

[Analyses of 77 patients with hemophagocytic syndrome].

OBJECTIVE: To summarize the clinical features and laboratory data of 77 patients with hemophagocytic syndrome (HPS). METHODS: A total of 77 patients of HPS were continuously collected from 2007 to 2014 at our hospital. Their underlying diseases, clinical features, laboratory data, therapy and prognosis were analyzed. RESULTS: Their The patients aged from 3 months to 85 years. The gender ratio was roughly equal. Primary HPS was diagnosed in only 5 cases by gene detection Another 72 cases belonged to secondary HPS. The causes were infection (n = 28), hematologic neoplasm (n = 25), autoimmune diseases (AID, n = 11) and unknown (n = 8). HPS was the initial symptom in nearly half cases of hematologic neoplasm and AID. HPS was characterized by high fever (100%), hypersplenomegaly (81.8%) and lymphadenopathy (40.3%). Laboratory data showed cytopenia (94.8%), serum ferritin elevation (93.2%), hypofibrinogenemia (61.8%), hemophagocytosis in bone marrow (78.1%) and hypertriglyceridemia (55.3%). Low NK-cell activity (95.2%) and elevation of sCD25 (100%) were specific manifestations in HPS. Pulmonary infection (36.4%) and hepatic malfunction (33.3%) were common. Approximately 70% were treated with HLH-2004. Pulse-dose corticosteroid therapy (methylprdnisolone 200-500 mg/d) was used in 8 AID patients. And 14 patients died and 10 withdrew treatment because of exacerbation. Five had complications of DIC and another 5 progressed into MODS. Neoplasm (52.0%) had the highest mortality in secondary HPS. And infection (25.0%) and AID (18.2%) followed. CONCLUSION: Sometimes HPS occurs simultaneously with autoimmune disease or neoplasm. Relevant laboratory tests for suspected patients may aid an early diagnosis. Presence of DIC or MODS in HPS is possibly correlated with a poor prognosis and a high mortality.

[Study on risk factors and behavior features related to chronic diseases among adults in Shanghai].

OBJECTIVE: To investigate the risk factors and behavior features related to chronic diseases among adults in Shanghai. METHODS: A total of 15 516 subjects aged over 18 years old were selected from the investigation project on chronic diseases and relevant risk factors in Shanghai in 2010. Questionnaire were used to investigate the general information of the subjects, such as behavior features as smoking, drinking, diet, physical activity as well as the prevalence and control of chronic diseases as hypertension and diabetes. The physical examination included height, weight, waist circumference, blood pressure, blood glucose and blood lipids. RESULTS: Being preprocessed by complex weighting method, the data showed that the overweight rate of Shanghai adults aged above 18 was 32.4% (5288), separately 32.2% (2506) and 32.5% (2782) (χ(2) = 0.10, P = 0.844) in urban and rural areas; the obesity rate was 8.8% (1538), separately 8.7% (738) and 8.8% (800) (χ(2) = 0.06, P = 0.901) in urban and rural areas. The overweight rate was separately 36.0% (2888) in males and 28.6% (2400) in females (χ(2) = 96.61, P < 0.01); while the obesity rate was separately 8.7% (745) in males and 8.9% (793) in females (χ(2) = 0.06, P = 0.851). Abdominal obesity rate was 44.3% (7419), separately 47.8% (3892) in males and 40.6% (3527) in females (χ(2) = 81.23, P < 0.01), 46.5% (3703) in urban areas and 42.6% (3716) in rural areas (χ(2) = 24.37, P = 0.069). Current smoking rate was 25.0% (3813), separately 48.4% (3722) and 1.2% (91) in males and females (χ(2) = 4572.06, P < 0.01); 23.6% (1609) and 26.0% (2204) in urban and rural areas (χ(2) = 11.92, P = 0.018). The regular smoking rate was 22.1% (3402). The rate of having the habit of drinking at least once a month in males was 39.5% (3102), separately 35.1% (1262) and 42.7% (1840) in urban and rural areas (χ(2) = 45.98, P = 0.012). The rate of drinking almost every day was 16.3% (1380), and the percentage of excessive alcohol consumption was 28.9% (2483). The percentage in group of subjects aging between 45-59 years old was 38.5% (1191), which was higher than that in any other groups (22.8% (641) in group aging 18-44 years old and 22.9% (651) in group aging ≥ 60 years old) (χ(2) = 241.38, P < 0.01). The percentage of over-drinking in rural area was higher than that in urban area, which was 33.5% (1578) and 22.8% (905) respectively (χ(2) = 117.12, P < 0.01). The percentage of once over-drinking was 11.3% (903). It was higher in group aging between 45-49 years old (15.3% (461)) than in other groups (9.0% (222) in group aging 18-44 years old and 8.2% (220) in group aging ≥ 60 years old) (χ(2) = 78.21, P < 0.01). It was also higher in rural area (13.5% (605)) than in urban area (8.3% (298)) (χ(2) = 51.74, P < 0.01). There were 75.0% (11 993) of the Shanghai adults never took physical activity. And the most important problems in dietary habit were insufficient intake of dairy products (98.0%, 15 218), vegetables (53.0%, 7864) and fruits (84.6%, 13 372), excess consumption of sodium (52.0%, 8257) and oil (51.7%, 7884). CONCLUSION: The risk factors of chronic diseases were highly prevalent in Shanghai. The prevalence of risk factors as overweight or obesity, lack of physical activity, smoking, over-drinking and unhealthy dietary habits were higher among adults living in suburban areas than those living in urban areas; the prevalence was also higher among the young adults than that among the elderly people, higher among males than that among females.

Therapeutic effects of NK-HDAC-1, a novel histone deacetylase inhibitor, on collagen-induced arthritis through the induction of apoptosis of fibroblast-like synoviocytes.

The purpose of this study is to investigate the therapeutic effects of a novel histone deacetylase inhibitor (HDACi), NK-HDAC-1, on collagen-induced arthritis (CIA) and pathogenic fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). The proliferation and apoptosis of FLSs treated with NK-HDAC-1 were evaluated by flow cytometry and fluorescence staining. The effect of NK-HDAC-1 treatment on pro-inflammatory cytokine production was determined by ELISA. CIA was established in DBA/1 mice, and NK-HDAC-1 or vehicle was administered daily after the onset of arthritis. Clinical and histological scores were calculated to assess the therapeutic efficacy of NK-HDAC-1. NK-HDAC-1 significantly inhibited the proliferation of FLSs through cell cycle arrest at the G2/M checkpoint and enhanced apoptosis of FLSs. The activity of caspases was increased during NK-HDAC-1 treatment. IL-6 production by FLSs was also suppressed by NK-HDAC-1. Furthermore, the oral administration of NK-HDAC-1 significantly enhanced synoviocyte apoptosis in vivo and inhibited CIA progression. Compared with subcroylanilide hydroxamic acid which exhibited moderate prophylactic efficacy, NK-HDAC-1 demonstrated therapeutic efficacy in CIA. NK-HDAC-1 is a novel HDACi that may ameliorate inflammatory arthritis by regulating the activation, apoptosis, and inflammatory responses of FLSs. This is the first study to support that NK-HDAC-1 may be a potential therapeutic agent for RA.

Obesity and overweight prevalence and its association with undiagnosed hypertension in Shanghai population, China: a cross-sectional population-based survey.

The aim of this study was to determine the prevalence of overweight and obese subjects in the Shanghai population of China and its association with undiagnosed hypertension, by taking age, gender and place of residence (urban or suburban) into account. A cross-sectional population-based survey was conducted in 2007. The sample included 13,359 participants aged 15-69 years.Weight, height, and blood pressure were recorded, and information about gender, age and place of residence was obtained. Overweight and obesity prevalence were calculated by the body mass index (BMI) definition recommended by Working Group on Obesity in China (normal weight, 18.5-23.9 kg/m(2); overweight, 24-27.9 kg/m(2); obesity, ≥ 28 kg/m(2)). Undiagnosed hypertension was defined by China criteria in accord with that of WHO-ISH (subjects with systolic pressure ≥ 140 mmHg, and/or diastolic pressure ≥ 90 mmHg). Multiple logistic regression analyses were used to assess the association of overweight or obesity with undiagnosed hypertension by adjusting for age, gender and place of residence. The overall overweight, obesity, and undiagnosed hypertension prevalence were 27.6% (95% CI: 26.8-28.4), 6.6% (95% CI: 6.2-7.0), and 15.5% (95% CI: 14.9-16.1), respectively. Compared to normal weight subjects, the odds ratios (OR) for subjects who were overweight and had hypertension was 2.33 (95% CI: 2.10-2.59); that for obesity and hypertension was 4.27 (95% CI: 3.66-4.99). These data suggest that overweight and obesity prevalence and their association with undiagnosed hypertension are high in our study population.