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Long non‑coding RNA (lncRNAs) have been identified to play important roles in multiple human diseases via the regulation of cell proliferation, cell invasion, or cell death. However, little is known about the role of lncRNAs in the process of shifts in the Th17/Treg ratio during the progression of juvenile idiopathic arthritis (JIA). The aim of the present study was to determine the role of lncRNA RP11‑340F14.6 in the shifting of the Th17/Treg ratio in JIA. The distribution of the T cell subgroup was detected by flow cytometry in peripheral blood mononuclear cells from patients with JIA and healthy controls. It was found that the expression of lncRNA RP11‑340F14.6 was upregulated, and to positively correlate with that of retinoic acid‑related orphan receptor gamma t (RORγt), and to negatively correlate with Foxp3 expression in patients with JIA. RP11‑340F14.6 induced the expression of its neighbor, P2X7R. Through a P2X7R‑independent approach, this lncRNA was also found to play a pivotal role in stimulating Th17 differentiation and simultaneously suppressing Treg distribution. Taken together, the findings of the present study demonstrate that RP11‑340F14.6 specifically binds to P2X7R, which results in the continuous activation of P2X7R. Thus, RP11‑340F14.6 may serve as a promising therapeutic target for the treatment of JIA.

Cryptococcosis is a potentially lethal disease that is primarily caused by the fungus Cryptococcus neoformans, treatment options for cryptococcosis are limited. Here, we show glucuronoxylomannan, the major polysaccharide component of C. neoformans, induces the recruitment of neutrophilic myeloid-derived suppressor cells in mice and patients with cryptococcosis. Depletion of neutrophilic myeloid-derived suppressor cells enhances host defense against C. neoformans infection. We identify C-type lectin receptor-2d recognizes glucuronoxylomannan to potentiate the immunosuppressive activity of neutrophilic myeloid-derived suppressor cells by initiating p38-mediated production of the enzyme arginase-1, which inhibits T-cell mediated antifungal responses. Notably, pharmacological inhibition of arginase-1 expression by a specific inhibitor of p38, SB202190, or an orally available receptor tyrosine kinase inhibitor, vandetanib, significantly enhances T-cell mediated antifungal responses against cryptococcosis. These data reveal a crucial suppressive role of neutrophilic myeloid-derived suppressor cells during cryptococcosis and highlight a promising immunotherapeutic application by inhibiting arginase-1 production to combat infectious diseases.

Background: Ulcerative colitis (UC) is a chronic, complicated, inflammatory disease with an increasing incidence and prevalence worldwide. However, the intrinsic molecular mechanisms underlying the pathogenesis of UC have not yet been fully elucidated.Methods: All UC datasets published in the GEO database were analyzed and summarized. Subsequently, the robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between UC patients and controls. Gene functional annotation and PPI network analysis were performed to illustrate the potential functions of the DEGs. Some important functional modules from the protein-protein interaction (PPI) network were identified by molecular complex detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), and analyses were performed. The results of CytoHubba, a plug for integrated algorithm for biomolecular interaction networks combined with RRA analysis, were used to identify the hub genes. Finally, a mouse model of UC was established by dextran sulfate sodium salt (DSS) solution to verify the expression of hub genes.Results: A total of 6 datasets met the inclusion criteria (GSE38713, GSE59071, GSE73661, GSE75214, GSE87466, GSE92415). The RRA integrated analysis revealed 208 significant DEGs (132 upregulated genes and 76 downregulated genes). After constructing the PPI network by MCODE plug, modules with the top three scores were listed. The CytoHubba app and RRA identified six hub genes: LCN2, CXCL1, MMP3, IDO1, MMP1, and S100A8. We found through enrichment analysis that these functional modules and hub genes were mainly related to cytokine secretion, immune response, and cancer progression. With the mouse model, we found that the expression of all six hub genes in the UC group was higher than that in the control group (P < 0.05).Conclusion: The hub genes analyzed by the RRA method are highly reliable. These findings improve the understanding of the molecular mechanisms in UC pathogenesis.

c-Cbl suppresses RelB activation to facilitate protective benefits of commensal fungi and maintain intestinal homeostasis., Intestinal fungi are critical for modulating host immune homeostasis and underlying mechanisms remain unclear. We show that dendritic cell (DC)–specific deficiency of casitas B-lineage lymphoma (c-Cbl) renders mice susceptible to dextran sodium sulfate (DSS)–induced colitis. Mechanistically, we identify that c-Cbl functions downstream of Dectin-2 and Dectin-3 to mediate the ubiquitination and degradation of noncanonical nuclear factor κB subunit RelB. Thus, c-Cbl deficiency in DCs promotes α-mannan–induced activation of RelB, which suppresses p65-mediated transcription of an anti-inflammatory cytokine gene, il10, thereby aggravating DSS-induced colitis. Moreover, suppressing fungal growth with fluconazole or inhibition of RelB activation in vivo attenuates colitis in mice with DC-specific deletion of c-Cbl. We also demonstrate an interaction between c-Cbl and c-Abl tyrosine kinase and find that treatment with DPH, a c-Abl agonist, synergistically increases fungi-induced c-Cbl activation to restrict colitis. Together, these findings unravel a previously unidentified fungi-induced c-Cbl/RelB axis that sustains intestinal homeostasis and protects against intestinal inflammation.

Macrophage activation syndrome (MAS) is a major cause of morbidity and mortality in pediatric rheumatology. We aimed to further understand the clinical features, treatment, and outcome of MAS in China. A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018. Eighty patients with MAS were enrolled, including 53 cases with systemic juvenile idiopathic arthritis (SJIA-MAS), 10 cases of Kawasaki disease (KD-MAS), and 17 cases of connective tissue disease (CTD-MAS). The clinical and laboratory data were collected before (pre-), at onset, and during full-blown stages of MAS. We compared the data among the SJIA-MAS, KD-MAS, and CTD-MAS subjects. 51.2% of patients developed MAS when the underlying disease was first diagnosed. In patients with SJIA, 22.6% (12/53) were found to have hypotension before the onset of SJIA-MAS. These patients were also found to have significantly increased aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as decreased albumin (P

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.

Exponential survival curves of early-passage human fibroblasts challenge classic biophysical models of cell inactivation. Thus, X-ray doses of 2-4 Gy inactivate normal, human skin fibroblasts in spite of negligible residual double-strand breaks. By contrast, radioresistant p53-mutant U251 glioblastoma cells proliferate in spite of residual damage. Similarly, p53 wildtype TK6 lymphoblastoid cells show exponential survival curves while the related p53-mutant WTK1 cell line continued to proliferate and showed a shouldered survival curve. Here, we propose a model in which the radioresistant shoulder region is due to tolerance to certain types or amounts of residual damage that would otherwise inactivate normal cells. Thus, the steeper initial slope and absence of a shoulder in the survival curve of normal cells may not imply a higher number of residual lesions but rather non-tolerance to these lesions.

Volatile anesthetics have been proven to treat experimental sepsis. Sevoflurane combined with oxygen is widely applied in the clinic, and our previous study indicated that this regimen significantly reduced sepsis-induced inflammatory responses and that inhibition of NF-κB pathway activation may contribute to this protection effect. Furthermore, our previous data has shown that sevoflurane combined with oxygen has prevention effect on sepsis-induced lung injury properties and bactericidal properties, but the mechanism is not well understood. Nitric oxide (NO) has been shown to have bactericidal effects and mitigating effects on lung injury, but this is not well studied in sepsis. The present study suggested that in cecal ligation and puncture (CLP)-induced sepsis, sevoflurane combined with oxygen had bactericidal effects and reduced neutrophil infiltration into the lung, preventing inflammatory lung injury. NO production was significantly induced in peritoneal lavage fluid and bronchoalveolar lavage fluid. These effects were abolished by pharmacological inhibition of nitric oxide synthase activity. Thus, our findings suggest that sevoflurane combined with oxygen exerts bactericidal effects and prevents lung injury in sepsis through the NO pathway.

Ionic liquid (IL)-assisted pretreatment is an important step in biochemical conversion of lignocellulosic biomass into biofuels. Design for low-cost ILs that efficiently work at a relatively low pretreatment temperature with a short processing time is of great interest. In this work, a functional acidic ionic liquid, 1-H-N-methyl-2-pyrrolidonium chloride ([Hnmp]Cl), was prepared by a simple synthetic procedure in a cost-effective manner and was then investigated for use in the pretreatment of lignocellulosic biomass. Factors including temperature, time, ratio of biomass to ionic liquid, and water content were studied to determine their impact on the pretreatment of lignocellulose; 91.39% of lignin content was recovered when the corn stalk was pretreated by pure [Hnmp]Cl at 100 °C for 45 min with a biomass loading of 5%. The highest glucose yield attained was 93.20% and the highest cellobiose yield was 18.76%, when the ratio of biomass to water was kept at 1:4. The pretreatment efficacy was dependent on the pretreatment temperature and processing time, which was more efficient for pure ionic liquid with respect to lignin recovery from lignocelluloses. However, more efficient enzymatic saccharification of cellulose-rich materials was achieved with aqueous ionic liquid.

Lignocellulosic biomass as a renewable and valuable resource has been a very active research area during recent years. Ionic liquids (ILs) are an attractive approach for the pretreatment of lignocelluloses. In this work, a series of pyrrolidinium-based ionic liquids were prepared simply and were investigated for the pretreatment of corn stalk at 90 °C for 30 min. The characteristics of regenerated lignin and cellulose-rich materials were determined by Fourier transform infrared spectroscopy (FTIR) analysis. Both ILs and ILs/H2O were studied. Notably, 10.17% lignin based on the original corn stalk was recovered with [Hmp]Cl-pretreatment; 21.34% and 15.83% reducing sugar based on the original corn stalk were observed during pretreatment with [Hmp]HSO4/H2O and [Hmp]Cl/H2O pretreatment, respectively; 80.54% of reducing sugar was obtained based on the cellulose-rich materials with [Hmp]Cl/H2O-pretreatment. Also, the glucose and cellobiose yields were 73.82% and 8.64%, respectively.

Lignocellulosic biomass is increasingly being promoted as an environmentally and economically sustainable fuel. However, the complex structure of lignocellulose makes it difficult to be fractionated, which limits its conversion into valuable products. In this work, a series of functional acidic ionic liquids (ILs) with a simple synthetic procedure were prepared. Fractionation of corn stover into cellulose, hemicellulose and lignin was successfully performed in ultrasound-assisted ILs at a low reaction temperature of 70 °C for 3 h followed by alkaline extraction. IL-isolated lignin, alkaline lignin, hemicellulose and cellulose were obtained in good yields and their chemical properties were analyzed by FTIR. Significantly, a good yield of IL-isolated lignin was obtained, which accounted for 60.48% of the original lignin. The IL-isolated lignin was S-G-H type indicating by 13C NMR and 13C–1H correlation 2D NMR (HSQC) analysis. Enzymatic hydrolysis of cellulose was performed successfully. A high yield of 97.77% reducing sugar was achieved. Glucose and cellobiose were measured by HPLC analysis, which accounted for 92.55% of cellulose conversion. Both of the hydrogen bond capability and the acidity of ILs contributed to achieve the effective fractionation. These ILs have a great potential for the preparation of biofuel.

Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase (Mincle/Syk) signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui (DU20) to Qubin (GB7) is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autologous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol (34.62 mg/kg), a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Mincle, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1β mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our results showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARD9, and interkeukin-1β. Moreover, this effect was similar to piceatannol. These findings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.

To observe the effect of penetrative needling of "Baihui" (GV 20) to "Qubin" (GB 7) on neurologic functions and expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and toll-like receptor 4 (TLR-4, involving in inflammatory reactions) in the tissue around the local cerebral hematoma in rats with intracerebral hemorrhage (ICH), so as to provide evidence for clinical treatment of ICH.Fifty-four male Wistar rats were randomly divided into sham control, mo-del and acupuncture groups, and then further divided into three time-point subgroups(1,3,7 days after modeling,After penetrative needling stimulation, the increased Longa's score and footfault asymmetry score in ICH rats were significantly decreased on day 1, 3 and 7 after modeling (Penetrative needling stimulation of GV 20 to GB 7 can reduce the levels of proinflammatory factors TNF-α and IL-6, and TLR-4 in the ICH tissues in rats with cerebral hemorrhage, which may contribute to its effect in improving neurological function.

Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated. Whether these mechanisms are beneficial or detrimental remains a matter of controversy, but there is no doubt as to their vital functions. An understanding of the mechanisms of injury and recovery after ICH is crucial to develop therapeutic strategies. In this review, we summarize the related studies and highlight the roles of autophagy, ER stress, and the UPR in disease, especially in ICH. We also provide an overview of therapeutic approaches that target autophagy, and we discuss the prospects for modulating autophagy, ER stress, and UPR mechanisms in ICH therapy.

Background: Intracerebral hemorrhage (ICH) is a life-threatening disease that confuses us for centuries. Acupuncture as a kind of Chinese traditional treatment has been empirically established and widely used in clinics in China, especially for stroke victims. Studies proved that GV20 penetrating GB7, a kind of needling manipulation, with which a needle is inserted into GV20 and then to GB7 under the scalp, is especially effective on the treatment of this disease. Wingless-type1 (Wnt1) is a key factor of Wnt/β-catenin signal pathway, which could promote regeneration and remodeling of neural function after ICH by affecting proliferation and differentiation of the neural stem cells (NSCs). The study on the expression of Wnt1 induced by GV20 penetrating GB7 may give out the theoretical principle of the treatment.Objective: The goal of this work is to observe the effect of GV20 penetrating GB7 needling on the protein/ mRNA expression of Wnt1 in brain tissue of ICH rats.Methods: In this experiment, we focused on observing the protein/mRNA expression level of Wnt1 by Western blot and real-time fluorescent quantitative PCR (RTFQ PCR) in the rats with ICH, which were treated by Dickkopfrelated protein 1 (DKK1), acupuncture or no intervention, comparing with the healthy rats without any treatment at fixed time points.Results: This study revealed that the expression of Wnt1 had the similar trend in all groups at each time point of corresponding treatment, which began to increase from the third day (3d), reached the peak on the seventh day (7d) then decreased gradually. The acupuncture treatment group showed a higher level of expression.Conclusion: The results show that GV20 penetrating GB7 has advantage on promoting the protein/mRNA expression of Wnt1, activates the intracellular Wnt pathway, and regulates the transcription of downstream target genes, affecting proliferation and differentiation of the neural stem cells (NSCs), thereby initiates endogenous repair mechanisms of the organism itself. This study provides a powerful scientific basis for acupuncture treatment on ICH.

Aim of the study Results of recent published studies on the association between the COX-2 8473T>C polymorphism and the risk of breast cancer have often been conflicting. To make a more precise estimation of the potential relationship, a meta-analysis was performed. Material and methods A total of seven case-control studies with 7,033 cases and 9,350 controls were included in the current meta-analysis through searching the databases of PubMed, Embase, and Cochrane Library (up to March 1st, 2013). The odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the strength of the association. The meta-analysis was conducted in a fixed/random effect model. Results We found no significant associations for all genetic models after all studies were pooled into the meta-analysis (for C vs. T: OR = 0.974, 95% CI: 0.906–1.047, p = 0.471; for CC vs. TT: OR = 0.957, 95% CI: 0.803–1.140, p = 0.62; for TC vs. TT: OR = 0.964, 95% CI: 0.881–1.055, p = 0.421; for CC + TC vs. TT: OR = 0.963, 95% CI: 0.880–1.053, p = 0.406; for CC vs. TT + TC: OR = 0.978, 95% CI: 0.831–1.15, p = 0.788). We also observed no obvious associations in the subgroup analyses by ethnicity (Caucasian) and source of controls (population based, PB) for all genetic models. Conclusions Current evidence suggests that the COX-2 8473T>C polymorphism is not associated with breast cancer risk.

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.

Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase (Mincle/Syk) signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui (DU20) to Qubin (GB7) is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autologous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol (34.62 mg/kg), a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Mincle, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1β mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our results showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARD9, and interkeukin-1β. Moreover, this effect was similar to piceatannol. These findings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.

The influence of human genetics on the natural history of hepatitis B virus (HBV) infection may be diminished in endemic areas because infection at a young age predisposes to chronic HBV infection. The present study aimed to address this issue through the determination of the influences of single nucleotide polymorphisms (SNPs) of myxovirus resistence-1 (MxA) -88 G/T and interferon (IFN)-gamma +874 A/T on the natural history of HBV infection in endemic regions. One hundred adult patients with self-limiting HBV infection (positive for both anti-HBs and anti-HBc) and 340 adult patients with persistent HBV infection were recruited from southern China, an endemic area with an HBsAg carrier rate of 17.8%. SNPs of MxA -88 G/T and interferon (IFN)-gamma +874 A/T were typed using a protocol based on competitively differentiated polymerase chain reaction. A highly significant difference in the distribution of MxA -88 G/T was observed between those with persistent and self-limiting HBV infections. The latter displayed a lower frequency of the GG genotype (41.0% vs. 52.9%, P = 0.036) and a higher frequency of the TT genotype (16.0% vs. 2.4%, P = 0.000), compared to patients with persistent infection. These differences were not gender- or age-specific. However, a significant distribution difference of IFN-gamma +874 A/T was not observed. Between two groups of patients, respectively, the distribution frequencies of the AA genotype (65.0% vs. 72.8%, P = 0.139) and the TT genotype (2.0% vs. 1.2%, P = 0.894) were found. These results suggest that MxA gene -88 G/T and IFN-gamma +874 A/T behave differently in endemic HBV infections. Further study is necessary to clarify the influences of human genetics on endemic HBV infections.

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.

Background: The influence of interleukin-10 (IL-10) gene promoter polymorphisms on the mode and sequel of HBeAg seroconversion (a favorable event usually) in patients with chronic Hepatitis B virus (HBV) infection has not been clarified. Patients and methods: IL-10 genotyping and haplotype analyses of 340 HBsAg carriers and 100 volunteers with self-limiting HBV infection from southern China, a high prevalent area of HBV were performed according to the single nucleotide polymorphisms in its promoter (−1082, −819 and −592) using a competitively differentiated PCR. Results: High-producer genotype (GG at −1082) or haplotype (GCC) was rarely found in patients from southern China (

Rapid, specific and sensitive methods without advanced equipment are required urgently in developing countries in order to detect or monitor lamivudine-resistant mutants routinely before or in the course of the therapy. A protocol is described for the detection of two major YMDD mutations simultaneously through modifying a previous competitively differentiated-PCR (CD-PCR) by revising the strategy, increasing the number of competitively differentiated primers, increasing the number of labeled haptens, optimizing the amplification system and analyzing its products by enzyme immunoassay. Special care was taken to promote the sensitivity, specificity and the ability of the protocol to detect mutation in mixture of the mutants and wild strain. YMDD mutants in clinical serum samples were detected simultaneously, specifically and rapidly only with assistance of the equipment used widely in highly prevalent areas of hepatitis B virus infection.

The aim of this study was to delineate the temporal and spatial sequence of STAT1 and STAT3 activation during development of GVHD following fully Major Histocompatibility Complex (MHC)-mismatched allogeneic Bone Marrow Transplantation (BMT). Activation of inflammatory signaling pathways in GVHD target organs was assessed by western blotting, phospho-flow cytometry and electromobility shift assays (EMSA). Development of GVHD was associated with significant expansion of phospho[p]-STAT1 and p-STAT3 expressing CD4+ T cells and CD8+ T cells. GVHD-specific STAT3/STAT1 activation preceded activation of Nuclear Factor-κB (NF-κB) and Mitogen Activated Protein Kinase (MAPK) and was associated with subsequent induction of STAT1 or STAT3-dependent inflammatory gene-expression programs (e.g. expression of IRF-1, SOCS1, IL-17). Our studies may help to establish a functional hierarchy of the signaling events leading to the development of GVHD and could be helpful in designing new molecularly targeted treatment approaches for GVHD.

This study aims to investigate the prognostic factors and long-term treatment outcome in patients with early stage nasal natural killer (NK)/T-cell lymphoma. Sixty-four patients were recruited in this study, whose clinical and laboratory data were collected from hospital records. Early stage (stage IE: 51, stage IIE: 13) nasal NK/T-cell lymphoma (NNTCL) was established according to Ann Arbor staging classification. Among these patients, 23 received radiotherapy (RT) alone, the remaining 41 cases were treated with radiochemotherapy (RCT) comprised of 1-6 cycles of anthracycline-based chemotherapeutic regimens. Results show that the median overall survival (OS) time was 41 months. The 5-year OS and progression-free survival rates were 59.2 and 52.3%, respectively. The 5-year OS rate for patients who received RT alone was 57.9%, whereas that for patients who received RCT was 61.5% (P = 0.47). There is no significant difference between two treatment modalities. Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (PS) score > or = 2, local tumor invasion out of nasal cavity, and lower complete remission (CR) rates in the initial treatment were significant unfavorable independent prognostic factors. Taken together, our study suggests that RCT did not improve the survival rate of patients with early stage NNTCL. PS score before treatment, local tumor invasion out of nasal cavity, and CR rate of the primary treatment may be independent prognostic factors among the subtype lymphoma entity.

As it is impossible for an active catheter with a very small space to accommodate overmany lead wires in minimally-invasive surgery, a matrix network system is presented, in this paper, to control SMA actuators using minimum lead wires. Pulse current is adjusted by pulse width modulation (PWM) signals from the single-chip processor. In addition, multiple SMA actuators' cooperation helps the active catheter to succeed in guiding motion.

To define the expression of single-chain variable fragment (ScFv) against hepatitis B virus core protein (HBc) mediated by recombinant replication defective adenovirus carrying the anti-HBc ScFv gene in vitro and to define the activity of anti-HBc ScFv combining HBcAg.The recombinant adenoviruses carrying anti-HBc ScFv gene generated by homologous recombination in bacteria and packaged in 293 cells were transfected into HepG2 cells, and the anti-HBc ScFv was detected using SDS-PAGE and Western blot.Green fluorescent protein (GFP) was observed in HepG2 cells after the transfection. SDS-PAGE displayed a protein strap about 2.7 x 10(4), and the result of Western blot displayed a positive reactive strap.Anti-HBc ScFv can be expressed in cells mediated by recombinant replication defective adenovirus carrying the anti-HBc ScFv gene.

To investigate the effects of c-myb antisense RNA on cell proliferation and the expression of c-myb, TGF-beta1 and beta1-I collagen in cultured hepatic stellate cells (HSC) from rats.Recombinant retroviral vector of c-myb antisense gene (pDOR-myb) was constructed, and then transfected into retroviral package cell line PA317 by means of DOTAP. The pseudoviruses produced from the resistant PA317 cells were selected with G418 to infect HSCs isolated from rat livers. The cell proliferation was measured by 3-[4, 5-Dimethylthiazolzyl]-2, 5-diphenyl tetrazo-dium bromide(MTT) method. The expression of c-myb, alpha (1)-I collagen and TGF-beta1 mRNA, and c-myb protein in HSCs was detected with semi-quantitive reverse transeription-polymerase chain reaction (RT-PCR) and Western-blot respectively.HSCs from rats were isolated successfully with the viability98%. In the pDOR-myb infected HSCs, the c-myb protein expression, cell proliferation,and alpha (1)-I collagen and TGF-beta1 mRNA expression were repressed significantly compared with their corresponding control groups (P0.01).c-myb plays a key role in activation and proliferation of HSC. c-myb antisense RNA can inhibit cell proliferation, alpha (1)-I collagen and TGF-beta1 mRNA expression, suggesting that inhibition of c-myb gene expression might be a potential way for the treatment of liver fibrosis.

To investigate the prevalence of hepatitis G virus (HGV) infection and to analyse the homology of different HGV strains in Southern China.A total of 1993 sera from different groups in Guangdong, Hong Kong, and Yunnan were detected by reverse transcription polymerase chain reaction (RT-PCR). The nucleotide sequences of 5'untranslated region (5'UTR) derived from 20 strains and NS5 region from 3 strains were determined.The positive rate of HGV RNA was 0.89 % in community population, 2.57 % in blood donors, 17.86 % in intravenous drug abusers, 14.13 % in patients with hemodialysis, 13.66 % in those with hepatocellular carcinoma, 25.30 % in non A-E hepatitis, 7.22 % in hepatitis B, 12.73 % in hepatitis C, 41.67 % in patients received bone marrow transplantation, respectively. The homology was 90.40-100 % in 5'UTR among different strains, while that of NS5 region was 93.3-94 % in nucleotide sequence, and 97-99.2 % in amino acid sequence.These results showed that there was a high incidence of HGV infection in patients from Southern China, being treated for bone marrow transplantation, hepatocellular carcinoma and those on haemodialysis. Furthermore, there was also a high frequency of co-infection of HGV with HBV, HCV, non A-E viral hepatitis and that among intravenous drug abusers. The study also showed that sequence variation in different strains was associated with geographical factors but there was no significant difference in 5'UTR in circulating viruses between different patient groups. Finally, by sequential analysis of viral species present in individual patients over a three months period there was no evidence of sequence variation in the 5' UTR.