Clinical features and prognosis of idiopathic inflammatory myopathies with coexistent multiple myositis-specific antibodies.

OBJECTIVES: This study aimed to evaluate the clinical significance of the coexistence of 2 or more myositis-specific antibodies (multiple MSAs) in adult patients with idiopathic inflammatory myopathies (IIM). METHODS: We assessed a cohort of 202 consecutive patients with IIM. Clinical features and survival rates were compared between patients with and without multiple MSAs. RESULTS: Of those 202 patients, 44 (21.8%) were found to have multiple MSAs. 63.6% of the 44 patients tested positive for anti-aminoacyl-tRNA synthetase antibodies (anti-ARS+) and 52.3% positive for anti-melanoma differentiation-associated protein-5 antibody (anti-MDA5+). The presence of multiple MSAs was associated with less rapidly progressive interstitial lung disease (RP-ILD), fever, rash, periungual erythema, more muscle involvement and dysphagia, higher albumin level, and higher positive rate of ANA antibody in anti-MDA5+ population. In anti-ARS+ population with multiple MSAs, there were more V-neck sign, skin ulcers, dysphagia and peripheral edema. No differences in survival rates were observed between patients with or without multiple MSAs in the overall and anti-ARS+ populations. However, the survival rate in anti-MDA5+ population with multiple MSAs was significantly higher than those without multiple MSAs (p = 0.003). Moreover, multiple MSAs remained an independent protective factor against mortality in multivariable Cox regression analysis of anti-MDA5+ population [HR 0.108 (95% CI 0.013, 0.908), p=0.041]. CONCLUSIONS: Multiple MSAs coexist in some IIM patients and their existence indicates mixed features from concomitant MSAs in anti-MDA5+ population and anti-ARS+ population. Identifying multiple MSAs could help to discover a more favourable disease phenotype with decreased mortality in anti-MDA5+ population.

Internalisation of neutrophils extracellular traps by macrophages aggravate rheumatoid arthritis via Rab5a.

OBJECTIVES: Although elevated levels of neutrophil extracellular traps (NETs) have been reported in patients with rheumatoid arthritis (RA), the role of NETs in RA and the relationship between NETs and macrophages in the pathogenesis of RA requires further research. Here, we sought to determine the role of NETs in RA pathogenesis and reveal the potential mechanism. METHODS: Neutrophil elastase (NE) and myeloperoxidase (MPO)-DNA were measured in human serum and synovium. NETs inhibitor GSK484 was used to examine whether NETs involved with RA progression. We stimulated macrophages with NETs and detected internalisation-related proteins to investigate whether NETs entry into macrophages and induced inflammatory cytokines secretion through internalisation. To reveal mechanisms mediating NETs-induced inflammation aggravation, we silenced GTPases involved in internalisation and inflammatory pathways in vivo and in vitro and detected downstream inflammatory pathways. RESULTS: Serum and synovium from patients with RA showed a significant increase in NE and MPO, which positively correlated to disease activity. Inhibiting NETs formation alleviated the collagen-induced arthritis severity. In vitro, NETs are internalised by macrophages and located in early endosomes. Rab 5a was identified as the key mediator of the NETs internalisation and inflammatory cytokines secretion. Rab 5a knockout mice exhibited arthritis alleviation. Moreover, we found that NE contained in NETs activated the Rab5a-nuclear factor kappa B (NF-κB) signal pathway and promoted the inflammatory cytokines secretion in macrophages. CONCLUSIONS: This study demonstrated that NETs-induced macrophages inflammation to aggravate RA in Rab 5a dependent manner. Mechanically, Rab5a mediated internalisation of NETs by macrophages and NE contained in NETs promoted macrophages inflammatory cytokines secretion through NF-κB-light-chain-enhancer of activated B cells signal pathway. Therapeutic targeting Rab 5a or NE might extend novel strategies to minimise inflammation in RA.

A retrospective cohort study in Chinese patients with adult polymyositis and dermatomyositis: risk of comorbidities and subclassification using machine learning.

OBJECTIVES: To identify the risk factors in Chinese patients with adult polymyositis and dermatomyositis for their comorbidities and explore a subclassification system. METHODS: Clinical records of 397 patients with idiopathic inflammatory myopathies were retrospectively reviewed. Logistic regression was used to identify potential risk factors for interstitial lung disease (ILD), other rheumatic diseases, and malignancy after bivariate analysis. Hierarchical clustering and decisional tree were utilised to identify subgroups and explore a subclassification system. RESULTS: A total of 119 polymyositis and 191 dermatomyositis patients were included. Anti-PM/Scl, anti-Ro52, anti-aminoacyl-tRNA synthetase and anti-MDA5 (adjusted odds ratios (AOR)=4.779, 1.917, 5.092 and 7.714 respectively) antibodies were risks (p<0.05), whereas overlapping malignancy was protective (AOR=0.107; p=0.002) for ILD across polymyositis, dermatomyositis and the total group. In subgroup models, Raynaud's phenomenon, arthralgia and semi-quantitative anti-nuclear antibody (AOR=51.233, 4.261, 3.047 respectively) were risks for other overlapping rheumatic diseases (p<0.05). For overlapping malignancy, male and anti-TIF1γ antibodies (AOR=2.533, 16.949) were risks (p<0.05), whereas disease duration and combination of ILD (AOR=0.954, 0.106) were protective in the total group (p<0.05); while anti-NXP2 antibodies were identified as risk factors (AOR=73.152; p=0.038) in polymyositis. Hierarchical clustering suggested a subclassification with 6 subgroups: malignancy overlapping dermatomyositis, classical dermatomyositis, polymyositis with severe muscle involvement, dermatomyositis with ILD, polymyositis with ILD, and overlapping of myositis with other rheumatic diseases. CONCLUSIONS: Accompanying ILD, other rheumatic diseases and malignancy are strongly associated with clinical manifestation and myositis-specific or myositis-associated autoantibodies among Chinese polymyositis and dermatomyositis patients. The subclassification system proposed a more precise phenotype defining toward stratified treatments.

[Classification of idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific antibodies].

OBJECTIVE: To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis. METHODS: We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed. RESULTS: A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia (P < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody (P < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (P=0.022) corresponding to antisynthetase syndrome (ASS). CONCLUSIONS: Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.

4-Hydroxy-7-oxo-5-heptenoic acid lactone is a potent inducer of brain cancer cell invasiveness that may contribute to the failure of anti-angiogenic therapies.

Previously, we discovered that free radical-induced oxidative fragmentation of the docosahexaenoate ester of 2-lysophosphatidylcholine produces 4-hydroxy-7-oxo-5-heptenoic acid (HOHA) lactone that, in turn, promotes the migration and invasion of endothelial cells. This suggested that HOHA lactone might similarly promote migration and invasion of glioblastoma multiformae (GBM) brain cancer stem cells (CSCs). A bioinformatics analysis of clinical cancer genomic data revealed that matrix metalloproteinase (MMP)1 and three markers of oxidative stress - superoxide dismutase 2, NADPH oxidase 4, and carbonic anhydrase 9 - are upregulated in human mesenchymal GBM cancer tissue, and that MMP1 is positively correlated to all three of these oxidative stress markers. In addition, elevated levels of MMP1 are indicative of GBM invasion, while low levels of MMP1 indicate survival. We also explored the hypothesis that the transition from the proneural to the more aggressive mesenchymal phenotype, e.g., after treatment with an anti-angiogenic therapy, is promoted by the effects of lipid oxidation products on GBM CSCs. We found that low micromolar concentrations of HOHA lactone increase the cell migration velocity of cultured GBM CSCs, and induce the expression of MMP1 and two protein biomarkers of the proneural to mesenchymal transition (PMT): p65 NF-κß and vimentin. Exposure of cultured GBM CSCs to HOHA lactone causes an increase in phosphorylation of mitogen-activated protein kinases and Akt kinases that are dependent on both protease-activated receptor 1 (PAR1) and MMP1 activity. We conclude that HOHA lactone promotes the PMT in GBM through the activation of PAR1 and MMP1. This contributes to a fatal flaw in antiangiogenic, chemo, and radiation therapies: they promote oxidative stress and the generation of HOHA lactone in the tumor that fosters a change from the proliferative proneural to the migratory mesenchymal GBM CSC phenotype that seeds new tumor growth. Inhibition of PAR1 and HOHA lactone are potential new therapeutic targets for impeding GBM tumor recurrence.

Transforming growth factor ß1 promotes fibroblast-like synoviocytes migration and invasion via TGF-ß1/Smad signaling in rheumatoid arthritis.

Migration and invasion are important characteristics of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), which are involved in joint damage and contribute to rheumatoid arthritis (RA) pathology. However, the underlying mechanisms remain unclear. Because epithelial-mesenchymal transition (EMT) is a key mechanism related to migration and invasion in cancer cells, we investigated the relationship between EMT and RA-FLSs and explored whether the transforming growth factor ß1 (TGF-ß1)/Smad signaling pathway is involved. In vivo, fibroblast-like synoviocytes (FLSs) were isolated from the synovium of RA or osteoarthritis (OA) patients and cultured for 4-8 passages. EMT markers were detected by immunofluorescence and Western blotting. RA-FLSs were treated with TGF-ß1 or Smad2/3 small interfering RNA (siRNA), EMT markers were detected, and migration and invasion were assessed by Transwell assays. EMT markers could be detected in FLSs; when compared with osteoarthritis fibroblast-like synoviocytes (OA-FLSs), E-cadherin and vimentin decreased, while N-cadherin and α-smooth muscle actin (α-SMA) increased in RA-FLSs. Furthermore, TGF-ß1 enhanced migration and invasion by inducing EMT via activating Smad2/3 in RA-FLSs. Phosphorylation of Smad2/3 was accompanied by degradation of Smad3. Silencing Smad2/3 blocked EMT and inhibited the migration and invasion induced by TGF-ß1. Matrix metalloproteinase 9 (MMP9) and vimentin were not affected when cells were treated with TGF-ß1 or Smad2/3 siRNA. The TGF-ß1/Smad signaling pathway is involved in EMT and contributes to migration and invasion in RA-FLSs. Interestingly, vimentin decreased in RA-FLSs, but there is no correlation between vimentin and TGF-ß1/Smad signaling pathway. Thus, further research on vimentin should be conducted.

Taxol alleviates collagen-induced arthritis in mice by inhibiting the formation of microvessels.

The objective of the present study is to evaluate the inhibitory effects of taxol (PTX) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. Collagen II (C II) and complete Freund's adjuvant (CFA) were used in C57BL/6 (H-2b) mice to generate the CIA model. Random grouping was performed in the normal control group, CIA model group, PTX 1.5 mg/kg group, PTX 1.0 mg/kg group, and PTX 0.5 mg/kg group. Arthritis index scores, tissue pathology scores, and synovium microvessel density (MVD) analysis were performed. Immunohistochemistry and enzyme-linked immunosorbent assay were used to detect the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-α (HIF-1α). The correlation between MVD and pathological scores and between MVD and the expression of VEGF as well as HIF-1α in the synovium were also evaluated. After PTX treatment, the three intervention group arthritis index scores were reduced when compared with the CIA group. The total histological scores in the three PTX treatment groups were lower than those in the CIA group. Similarly, PTX significantly alleviated the scores for synovitis, pannus formation, and bone destruction. Compared with the CIA group, the MVD of the three intervention groups decreased in a dose-dependent manner. The expression of VEGF and HIF-1α in synovial tissues and serum also significantly decreased after PTX treatment. Further analysis showed that MVD and pathological scores and MVD and expression of VEGF as well as HIF-1α in the synovium were positively correlated. PTX may alleviate CIA by suppressing angiogenesis, providing new insights into the treatment of rheumatoid arthritis (RA). VEGF and HIF-1α may be targets for PTX suppression of microvessel formation.

High-resolution dynamic oxygen-17 MR imaging of mouse brain with golden-ratio-based radial sampling and k-space-weighted image reconstruction.

PURPOSE: The current study aimed to develop a three-dimensional (3D) dynamic oxygen-17 (17 O) MR imaging method with high temporal and spatial resolution to delineate the kinetics of 17 O water uptake and washout in the brains of mice with glioblastoma (GBM). METHODS: A 3D imaging method with a stack-of-stars golden-ratio-based radial sampling scheme was employed to acquire 17 O signal in vivo. A k-space-weighted image reconstruction method was used to improve the temporal resolution while preserving spatial resolution. Simulation studies were performed to validate the method. Using this method, the kinetics of 17 O water uptake and washout in the brains of mice with GBM were delineated after an intravenous bolus injection of 17 O water. RESULTS: The proposed 17 O imaging method achieved an effective temporal resolution of 7.56 s with a nominal voxel size of 5.625 µL in the mouse brain at 9.4 T. Reduced uptake and prolonged washout of 17 O water were observed in tumor tissue, suggesting compromised cerebral perfusion. CONCLUSION: This study demonstrated a promising dynamic 17 O imaging approach that can delineate 17 O water kinetics in vivo with high temporal and spatial resolution. It can also be used to image cerebral oxygen consumption rate in oxygen-17 inhalation studies. Magn Reson Med 79:256-263, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Hard templating ultrathin polycrystalline hematite nanosheets: effect of nano-dimension on CO2 to CO conversion via the reverse water-gas shift reaction.

Understanding how nano-dimensionality impacts iron oxide based catalysis is central to a wide range of applications. Here, we focus on hematite nanosheets, nanowires and nanoparticles as applied to catalyze the reverse water gas shift (RWGS) probe reaction. We introduce a novel approach to synthesize ultrathin (4-7 nm) hematite nanosheets using copper oxide nanosheets as a hard template and propose a reaction mechanism based on density functional theory (DFT) calculations. Hematite nanowires and nanoparticles were also synthesized and characterized. H2 temperature programmed reduction (H2-TPR) and RWGS reactions were performed to glean insights into the mechanism of CO2 conversion to CO over the iron oxide nanomaterials and were compared to H2 binding energy calculations based on density functional theory. While the nanosheets did exhibit high CO2 conversion, 28% at 510 °C, we found that the iron oxide nanowires had the highest CO2 conversion, reaching 50% at 750 °C under atmospheric pressure. No products besides CO and H2O were detected.

2-(ω-Carboxyethyl)pyrrole Antibody as a New Inhibitor of Tumor Angiogenesis and Growth.

BACKGROUND: Angiogenesis is a fundamental process in the progression, invasion, and metastasis of tumors. Therapeutic drugs such as bevacizumab and ranibuzumab have thus been developed to inhibit vascular endothelial growth factor (VEFG)-promoted angiogenesis. While these anti-angiogenic drugs have been commonly used in the treatment of cancer, patients often develop significant resistance that limits the efficacy of anti-VEGF therapies to a short period of time. This is in part due to the fact that an independent pathway of angiogenesis exists, which is mediated by 2-(ω-carboxyethyl)pyrrole (CEP) in a TLR2 receptor-dependent manner that can compensate for inhibition of the VEGF-mediated pathway. AIMS: In this work, we evaluated a CEP antibody as a new tumor growth inhibitor that blocks CEP-induced angiogenesis. METHOD: We first evaluated the effectiveness of a CEP antibody as a monotherapy to impede tumor growth in two human tumor xenograft models. We then determined the synergistic effects of bevacizumab and CEP antibody in a combination therapy, which demonstrated that blocking of the CEP-mediated pathway significantly enhanced the anti-angiogenic efficacy of bevacizumab in tumor growth inhibition indicating that CEP antibody is a promising chemotherapeutic drug. To facilitate potential translational studies of CEP-antibody, we also conducted longitudinal imaging studies and identified that FMISO-PET is a non-invasive imaging tool that can be used to quantitatively monitor the anti-angiogenic effects of CEP-antibody in the clinical setting. RESULTS: That treatment with CEP antibody induces hypoxia in tumor tissue WHICH was indicated by 43% higher uptake of [18F]FMISO in CEP antibody-treated tumor xenografs than in the control PBS-treated littermates.

Estimated cancer incidence and mortality in Hebei province, 2012.

OBJECTIVE: This study estimates the numbers of new cancer cases and cancer deaths in Hebei province using incidence and mortality data from 9 population-based cancer registries in 2012. METHODS: The data of new diagnosed cancer cases and cancer deaths in 2012 were collected from 9 population-based cancer registries of Hebei province in 2015. All the data met the National Central Cancer Registry of China (NCCR) criteria of data quality. The pooled data analysis was stratified by areas (urban/rural), gender, age group (0, 1.4, 5.9, 10.14, …, 85+) and cancer type. New cancer cases and deaths in Hebei province were estimated using age-specific rates and corresponding provincial population in 2012. The 10 most common cancers in different groups and the cumulative rates were calculated. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. RESULTS: All cancer registries covered 4,986,847 populations, 6.84% of Hebei provincial population (2,098,547 in urban and 2,888,300 in rural areas). The percentage of cases morphologically verified (MV%) and death certificate-only cases (DCO%) were 76.40% and 4.72%, respectively. The mortality to incidence rate ratio (M/I) was 0.64. In 2012, it is estimated that there were about 187,900 new diagnosed cancer cases and 119,800 cancer deaths in Hebei province. The incidence rate of cancer was 258.12/100,000 (275.75/100,000 in males, 239.78/100,000 in females), and the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 210.65/100,000 and 208.50/100,000, with the cumulative incidence rates (0.74 years old) of 24.46%. The cancer incidence and ASIRC were 256.99/100,000 and 211.32/100,000 in urban areas and 258.94/100,000 and 209.99/100,000 in rural areas, respectively. The cancer mortality rate was 164.63/100,000 (201.85/100,000 in males, 125.92/100,000 in females). Agestandardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 137.30/100,000 and 137.39/100,000 with the cumulative mortality rate (0.74 years old) of 14.58%, respectively. The cancer mortality rate in rural areas (167.16/100,000) was higher than that in urban areas (161.16/100,000). The most common cancers were lung cancer, stomach cancer, breast cancer, esophageal cancer, liver cancer and colorectal cancer, which accounted for 72.31% of all cancer cases. Lung cancer, stomach cancer, liver cancer, esophageal cancer and colorectal cancer were the major causes of cancer death in Hebei province, which accounted for 75.24% of all cancer deaths. The cancer spectrum differs between urban and rural, males and females in both incidence and mortality rates. CONCLUSIONS: The most common cancers were lung cancer, stomach cancer, esophageal cancer, breast cancer, liver cancer and colorectal cancer in Hebei province.

[Interferon-ß combined with all-trans retinoic acid supresses proliferation and promote apoptosis by inhibiting JAK2/STAT3 pathway in HepG2 human hepatocellular carcinoma cells].

Objective To investigate the effect of interferon-ß (IFN-ß) combined with all-trans retinoic acid (ATRA) on the proliferation and apoptosis of HepG2 human hepatocarcinoma cells and the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal pathway in the process. Methods HepG2 cells were randomly divided intro three groups and treated with 1000 U/mL IFN-ß, 10 µmol/L ATRA and 1000 U/mL IFN-ß combined with 10 µmol/L ATRA, respectively for 24 hours. Cell viability was measured by MTT assay and apoptosis rate was detected by flow cytometry. Western blotting was applied to detect the protein levels of p-JAK2, p-STAT3, gene associated with retinoid-interferon-induced mortality-19 (GRIM-19), Bcl-2, Bcl-xl and Bax. Results IFN-ß or ATRA inhibited the proliferation and induced the apoptosis of HepG2 cells. The effect was enhanced when IFN-ß was combined with ATRA. The expressions of p-JAK2 and p-STAT3 were down-regulated while the expressions of GRIM-19 and Bax were up-regulated after treated with IFN-ß or ATRA on HepG2 cells, especially the combination of IFN-ß and ATRA. Conclusion Combination of IFN-ß and ATRA could suppress the proliferation and induced the apoptosis of HepG2 hepatocarcinoma cells by inhibiting JAK2/STAT3 signal pathway.

[Incidence and mortality of cancers appeared in the Hebei provincial cancer registry system in 2011].

OBJECTIVE: To analyze the cancer incidence and mortality in Hebei cancer registry available areas in 2011. METHODS: Data were collected from 8 population-based cancer registries systems in Hebei province. Incidence and mortality rates stratified by areas (urban/rural), sex, age group and cancer site were analyzed. 10 common cancers in different groups, proportions and cumulative rates were calculated. The Chinese population census in the year 2000 and Segi's populations were used for age-standardized incidence/mortality rates. RESULTS: In all the 8 cancer registries that covering a total of 4 573 293 population (2 139 779 in urban and 2 433 514 in rural areas), data was used for the analysis. The total new cancer incidence cases and deaths were 11 269 and 7 477, respectively. All the morphologically verified cancer cases (MV%) accounted for 75.26% while 3.85% of the incident cases were identified only through death certification records (DCO%). The mortality to incidence ratio appeared as 0.66. The crude incidence appeared in the Hebei cancer registration areas was 246.41/105 (264.55/105 in males and 227.75/105 in females). The age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) appeared as 207.13/105 and 206.61/105 respectively, with the cumulative incidence rates as (0-74 age years old) 23.57%. The cancer incidence and ASIRC were 242.64/105 and 200.19/105 in urban areas, whereas 249.72/105 and 214.11/105, respectively in rural areas. The crude mortality in Hebei cancer registration areas was 163.49/105 (196.54/105 in male, 129.51/105 in female), with age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) as 144.48/105 and 147.69/105. The cumulative mortality rate (0-74 age years old) was 14.71%. The cancer mortality (167.91/105) in rural areas seemed higher than the mortality (158.47/105) in urban areas. The most common sites of cancers were: stomach, lung, esophagus, breast, liver and colorectal, which accounted for 71.66% of all the cancer cases. Lung cancer, stomach cancer, esophagus cancer, liver cancer and colorectal cancer were the major causes responsible for the cancer deaths in the areas with data of cancer registration, which accounted for 74.79% of all the cancer deaths. CONCLUSION: The coverage of Hebei cancer registration population could reflect the cancer burden in various areas and populations. The most commonly seen cancers were stomach, lung, esophagus, breast, liver, and colorectal, in Hebei province. In order to reduce the burden of cancers, prevention and control measures should be strengthened.

Single nucleotide polymorphisms in the tumor necrosis factor-alpha gene promoter region alter the risk of psoriasis vulgaris and psoriatic arthritis: a meta-analysis.

BACKGROUND: It has been confirmed that tumor necrosis factor-alpha (TNFα), a macrophage-derived pro-inflammatory cytokine, plays an important role in the pathogenesis of psoriasis vulgaris and psoriatic arthritis (PsV&PsA). In contrast, the reported association of TNFα gene promoter region single nucleotide polymorphisms (SNPs) and PsV&PsA has remained controversial. Accordingly, we performed a meta-analysis to provide new evidence that SNPs in the TNFα gene promoter region alter not only the risk of psoriasis vulgaris (PsV) or psoriatic arthritis (PsA) but also of PsV&PsA. METHODS: Interrelated literature dated to October 2012 was acquired from the PubMed, ScienceDirect, and SpringerLink databases. The number of the genotypes and/or alleles for the TNFα promoter in the PsV and PsA and control subjects was obtained. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate the risk of PsV and/or PsA with TNFα promoter SNPs. RESULTS: A total of 26 papers of 2159 for PsV (2129 normal controls) and 2360 for PsA (2997 normal controls) were included in our meta-analysis. The results showed that the variant genotype and allele of TNFα -308A/G was protective in pooled groups of patients with PsV&PsA (OR = 0.682, 0.750; 95% CI, 0.596-0.779, 0.653-0.861). However, the variant genotypes and alleles of TNFα -238A/G and -857T/C had an increased risk of PsV&PsA (OR = 2.493, 2.228, 1.536, 1.486, 95% CI, 1.777-3.498, 1.628-3.049, 1.336-1.767, 1.309-1.685). Moreover, the meta-analysis revealed a significant association between TNFα -238A/G and -857T/C polymorphism and PsA susceptibility (OR = 2.242, 2.052, 1.419, 1.465; 95% CI, 1.710-2.941, 1.614-2.610, 1.214-1.658, 1.277-1.681). In contrast, the variant genotypes and alleles of TNFα -308A/G proved to be protective against PsV (OR = 0.574, 0.650, 95% CI, 0.478-0.690, 0.556-0.759), whereas TNFα -238A/G was found to have a risk association (OR = 2.636, 2.223, 95% CI, 1.523-4.561, 1.317-3.751). CONCLUSIONS: SNPs in the TNFα gene promoter region alter the risk of PsV and/or PsA.

Liver cancer mortality trends during the last 30 years in Hebei province: comparison results from provincial death surveys conducted in the 1970's, 1980's, 1990's and 2004-2005.

BACKGROUND AND AIMS: Liver cancer is a major health problem in low-resource countries. Approximately 55% of all liver cancer occurs in China. Hebei Province is one of the important covering nearly 6% of the population of China. The aim of this paper was to explore liver cancer mortality trends during past 30 years, and provide basic information on prevention strategies. METHODS: Hebei was covered covered all the three national surveys during 1973-1975, 1990-1992, and 2004-2005 and one provincial survey during 1984-1986. Subjects included all cases dying from liver cancer in Hebei Province. Liver cancer mortality trend and geographic differences across cities and counties were analyzed. RESULTS: There were 82,878 deaths in Hebei Province during 2004-2005 with an average mortality rate was 600.9/10,000, and an age-adjusted rate of 552.3/10,000. Those dying of cancer were 18,424 cases, accounting for 22.2% of all deaths, second only to cerebrovascular disease as a cause of death. Cancer mortality was 133.6/100,000 (age-adjusted rate was 119.2/100,000). Liver cancer ranked fourth in this survey with a mortality rate of 21.0/100,000, 28.4/100,000 in males and 13.35/10,000 in females, accounting for 15.7%, 17.1% and 13.4% of the total number of cancer deaths and in males and females, respectively. The sex ratio was 2.13. Since the 1970s, liver cancer deaths of Hebei province have been increasing slightly. The crude mortality rates in the four surveys were 11.3, 16.0, 17.4, 21.0 per 100,000, respectively, with age-adjusted rates fluctuating during the past 30 years, but the trend also being upwards. There is a tendency for the mortality rates to be higher in coastal than mountain areas, and is relative lower in the plain area, with crude mortality rates of 25.3, 22.1, and 19.1 per 100,000, respectively. There were no notable differences in cride data between urban and rural, but the age-adjusted mortality rate in rural was much higher. CONCLUSION: Our study indicated that the mortality of liver cancer in Hebei Province is lower than the national average level. There is a slightly increase trend, especially in some counties. Liver cancer is a major health problem and it is necessary to further promote prevention strategies in Hebei province.

Longitudinal near-infrared imaging of myelination.

Myelination is one of the fundamental biological processes in the development of vertebrate nervous system. Disturbance of myelination is found to be associated with progression in many neurological diseases such as multiple sclerosis. Tremendous efforts have been made to develop novel therapeutic agents that prevent demyelination and/or promote remyelination. These efforts need to be accompanied by the development of imaging tools that permit direct quantification of myelination in vivo. In this work, we describe a novel near-infrared fluorescence imaging technique that is capable of direct quantification of myelination in vivo. This technique is developed based on a near-infrared fluorescent probe, 3,3'-diethylthiatricarbocyanine iodide (DBT) that readily enters the brain and specifically binds to myelinated fibers. In vivo imaging studies were first conducted in two animal models of hypermyelination and hypomyelination followed by longitudinal studies in the cuprizone-induced demyelination/remyelination mouse model. Quantitative analysis suggests that DBT is a sensitive and specific imaging probe of myelination, which complements other current myelin-imaging modalities and is of low cost.