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Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood driven by aberrant pathways of T-cell activation. T helper 17 (Th17)/regulatory T cell (Treg) imbalance plays critical roles in the pathogenesis of arthritis. MicroRNA-125b (miR-125b) was upregulated after the activation of the initial CD4+ T cells, and could regulate the differentiation of CD4+ T cells. However, the effects of miR-125b on Th17/Treg imbalance and differentiation of Th17/Treg cells remain unknown. In this study, we evaluated the expression of miR-125b in the peripheral blood mononuclear cells (PBMCs) of children with JIA, and the relationship of miR-125b with Th17/Treg imbalance. Then, we used lentivirus vector-mediated overexpression technology to investigate the regulatory function of miR-125b in CD4+ T cells or dendritic cell/CD4+ T co-culture system. Decreased miR-125b expression in PBMCs and CD4+ T cells of JIA patients was negatively correlated with the ratio of Th17/Treg cells. It also correlated negatively with retinoic acid receptor-related orphan receptor γt but positively with Forkhead box protein 3 at transcriptional levels. Furthermore, we found that miR-125b overexpression inhibited Th17 cell differentiation, whereas facilitated the differentiation of Treg cells. MiR-125b upregulation led to the decrease of Th17-secreting cytokines but the increase of the Treg-secreting cytokines. Our results demonstrate that miR-125b participated in regulating Th17/Treg cell differentiation and imbalance in JIA patients. These findings provide novel insight into the critical role of miR-125b in the Th17/Treg imbalance of JIA, and raise the distinct possibility that miR-125b may prove to be a potential therapeutic target for JIA.

Background: X-Linked Agammaglobulinemia is a disease of the immune system in which there is defective development of the B lymphocytes due to which the production of gammaglobulins is markedly reduced; which results in immunodeficiency and high vulnerability to contract fatal infections. This is the reason for which a patient with XLA presents with history of recurrent infections. XLA is known to be caused due to a mutation in the Btk gene. Btk gene mutation observed on gene mapping markedly reduced levels of B lymphocytes and immunoglobulins; are the confirmatory laboratory findings for the diagnosis of XLA. As there is immunodeficiency in the patient, this condition is treated with intravenous immunoglobulin therapy. In this article, two cases with XLA have been described. Over a period of one month, two cases of XLA were admitted at the hospital. This is to pay attention to the fact that XLA is a rare condition, accounting to 1 in 200,000 live births. In view of its rarity, the two cases have been reported ahead in the article. Methods: Two patients who were a known case of X-Linked Agammaglonulinemia were reviewed in detail. Their records were reviewed and appropriate clinical data collected. The serum levels of immunoglobulins and B lymphocytes of these patients were thoroughly evaluated. BTK gene screening was also analysed to confirm the diagnosis of XLA. Results: Two patients who were previously diagnosed with XLA came to our hospital with complaints of recurrent respiratory tract infections. One patient, a 12 years old boy admitted with complaints of cough with expectoration and fever, was found to have low levels of B lymphocytes, IgM and IgA. His mother and elder brother were already diagnosed with XLA. The second patient , a 10 years old boy who got admitted at the hospital with fever and cough, has low levels of B lymphocytes, IgM and IgA, Genescreening showed BTK gene mutation. His mother is a known case of XLA confirmed with BTK genemutation on screening. Conclusion: The two cases mentioned above represent X-Linked Agammaglobulinemia, which is a rare disease with an occurrence rate of 1 in 200,000 live births. These two cases were reported at our hospital within duration of two weeks. Paying attention to the fact of the rarity of this condition, the admission of two patients with a rare disease as XLA, within such a short duration of time, claims the consideration of these cases to be reported. Implications on detecting female carriers in the family, counselling of the family members, and early diagnosis and treatment of affected males in the family ; are all important aspects associated with the diagnosis of XLA in a patient.

By using printability tester for printing on ordinary white cardboard and light beam hologram paper, measuring spectral information and chrominance information of the two samples, and then perform spectral fitting by analyses their color characteristics, The aim of this research was to propose one method for color calculation of printing on light beam hologram papers, according to the color information of ordinary white cardboard.

A case-control study was performed to ascertain clinical features of children who had been diagnosed as Kawasaki disease shock syndrome (KDSS), a severe condition related to Kawasaki disease (KD). Hospitalized patients were selected in Nanjing Children's Hospital. Demographic characteristics, clinical presentation, laboratory data, cardiovascular findings, and therapies were analyzed. Compared with the control group, KDSS patients were older and had more serious skin rash. The proportions of leukocytosis, neutrophilia, and hypoalbuminemia was higher, as was the level of while blood cell count, C-reactive protein, brain natriuretic peptide, and ferroprotein. KDSS patients had higher incidence of arrhythmias and more severe coronary artery involvement. All case patients received aspirin, glucocorticoid, and intravenous immunoglobulin, 33.3% required albumin, and 90.4% needed vasoactive infusions. In conclusion, KDSS patients may have more serious inflammatory responses in the acute phase. Short-term use of glucocorticoid may be important in inhibiting the inflammatory response. Albumin and vasoactive drugs are useful to rescue shock.

Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4+ T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6). Exposure to CII induced the elevation of mRNAs encoding retinoic acid receptor-related orphan receptor α and γt, which were abolished by pretreatment with P2X7R antagonists. Furthermore, blocking P2X7R signaling abolished the CII-mediated increase in IL-17A. Blockade of P2X7R remarkably inhibited hind paw swelling and ameliorated pathological changes in ankle joint of the collagen-induced arthritis mice. Thus, we demonstrated a novel function for P2X7R signaling in regulating CII-induced differentiation of Th17 cells. P2X7R signaling facilitates the development of the sophisticated network of DC-derived cytokines that favors a Th17 phenotype.

e13062Background: Circulating tumor cells (CTCs) are rare tumor cells disseminated in peripheral blood from either original tumor sites or metastatic sites. Current studies on CTCs are mainly focus...

Juvenile idiopathic arthritis (JIA) is a common autoimmune disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The protein tyrosine phosphatase nonreceptor 22 (PTPN22) and signal transducer and activator of transcription factor 4 (STAT4) have been recognized as susceptibility genes for numerous autoimmune diseases. Associations of STAT4 rs7574865 G/T and PTPN22 (rs2488457 G/C and rs2476601 C/T) polymorphisms with JIA have repeatedly been replicated in several Caucasian populations. The aim of this study was to investigate the influence of three polymorphisms mentioned above on the risk of developing JIA in Han Chinese patients. Genotyping was performed on a total of 137 Chinese patients with JIA (JIA group) and 150 sex and age frequency-matched healthy volunteers (Control group). The single-nucleotide polymorphisms (SNP) were determined by using direct sequencing of PCR-amplified products. There were significant differences of PTPN22 rs2488457 G/C and STAT4 rs7574865 G/T polymorphisms between both groups. However, no significant difference was observed in distribution frequencies of PTPN22 rs2476601 polymorphism. The association with the PTPN22 rs2488457 G/C polymorphism remained significant in the stratifications by age at onset, ANA status, splenomegaly, lymphadenectasis and involvement joints. As with the STAT4 rs7574865 G/T polymorphisms, the enthesitis-related arthritis and presence of hepatomegaly had strong effect on the association. Our data strengthen STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms as susceptibility factors for JIA.

This study attempts to characterize the clinical features of various subtypes of juvenile idiopathic arthritis (JIA) and try to investigate the prognostic factors. Patients with JIA hospitalized in Nanjing Children Hospital during April 2005 to April 2010 were enrolled. Clinical manifestations and laboratory parameters were retrospectively reviewed. A total of 202 cases were included, 105 males and 97 females, with average age at onset of 7.5 years. Patients with systemic JIA were most common, accounting for 47.0 %. Fever, rash, and arthritis were the most common clinical manifestations. The most commonly involved joints were the knee and ankle. Laboratory parameters were significantly different but not specific. Time from onset to treatment, hepatomegaly, and involvement of wrist may have a significant effect on the outcome. A total of 117 cases were followed up, with an average follow-up time of 2 years. Among them, 55 cases achieved complete remission, 27 cases with partial remission, and 29 cases without remission, and six died. JIA is a heterogeneous disease with varied onset and clinical manifestations, which makes treatment a serious challenge. Receiving treatment late, hepatomegaly, and impaired wrist were early risk factors for an unfavorable outcome.