OBJECTIVE We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. METHODS Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American–European Consensus Group (AECG) criteria, a model-based “gold standard”obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Background:The possible presence of early tumour dissemination is the rationale behind the use of systemic adjuvant chemotherapy in patients with operable breast cancer. Circulating tumour cells (CTC) in peripheral blood may represent the possible presence of early tumour dissemination. However, relatively few studies were designed to investigate the relationship between the change of CTC status and the efficacy of adjuvant chemotherapy in operable breast cancer patients.Methods:In a prospective study, we established a multimarker real-time quantitative PCR platform to detect CTC in peripheral blood of breast cancer patients. By using this platform, we detected CTC in peripheral blood of 94 operable breast cancer patients. Control group consisted of 20 patients with benign breast disease and 20 healthy volunteers. For 72 patients who underwent systemic adjuvant chemotherapy, the dynamic CTC status at three different time points (1 day before initiation of chemotherapy, 1 week after three cycles of chemotherapy and 1 week after all cycles of chemotherapy) was observed.Results:Circulating tumour cells were detected in 56%(53 out of 94) of patients with operable breast cancer. The specificity was 95%. Seventy-two patients who received systemic adjuvant chemotherapy were followed up. After three cycles of chemotherapy, 47%(18 out of 38) of patients who were CTC-positive before chemotherapy changed into negative status. In addition, another 5%(2 out of 38) of patients had changed into negative status after all cycles of chemotherapy.Conclusion:Systemic adjuvant chemotherapy had a significant impact on CTC status, and this effect could be observed after three cycles of chemotherapy. Circulating tumour cells detection had the potential to be used to evaluate the efficacy of systemic adjuvant chemotherapy immediately after the chemotherapy was finished in operable breast cancer patients.British Journal of Cancer advance online publication, 19 April 2012; doi:10.1038/bjc.2012.157 www.bjcancer.com.

Strong Lewis acids of air-stable metallocene bis(perfluorooctanesulfonate)s [M(Cp)(2)][OSO(2) C(8) F(17)](2) ⋅nH(2) O⋅THF (M=Zr (2 a⋅3 H(2) O⋅THF), M=Ti (2 b⋅2 H(2) O⋅THF)) were synthesized by the reaction of [M(Cp)(2)]Cl(2)(M=Zr (1 a), M=Ti (1 b)) with nBuLi and C(8) F(17) SO(3) H (2 equiv) or with C(8) F(17) SO(3) Ag (2 equiv). The hydrate numbers (n) of these complexes were variable, changing from 0 to 4 depending on conditions. In contrast to well-known metallocene triflates, these complexes suffered no change in open air for a year. thermogravimetry-differential scanning calorimetry (TG-DSC) analysis showed that 2 a and 2 b were thermally stable at 300 and 180 °C, respectively. These complexes exhibited unusually high solubility in polar organic solvents. Conductivity measurement showed that the complexes (2 a and 2 b) were ionic dissociation in CH(3) CN solution. X-ray analysis result confirmed 2 a⋅3 H(2) O⋅THF was a cationic organometallic Lewis acid. UV/Vis spectra showed a significant red shift due to the strong complex formation between 10-methylacridone and 2 a. Fluorescence spectra showed that the Lewis acidity of 2 a fell between those of Sc(3+)(λ(em)=474 nm) and Fe(3+)(λ(em)=478 nm). ESR spectra showed the Lewis acidity of 2 a (0.91 eV) was at the same level as that of Sc(3+)(1.00 eV) and Y(3+)(0.85 eV), while the Lewis acidity of 2 b (1.06 eV) was larger than that of Sc(3+)(1.00 eV) and Y(3+)(0.85 eV). They showed high catalytic ability in carbonyl-compound transformation reactions, such as the Mannich reaction, the Mukaiyama aldol reaction, allylation of aldehydes, the Friedel-Crafts acylation of alkyl aromatic ethers, and cyclotrimerization of ketones. Moreover, the complexes possessed good reusability. On account of their excellent catalytic efficiency, stability, and reusability, the complexes will find broad catalytic applications in organic synthesis.

Gastrointestinal stromal tumors (GISTs) occur in diverse locations of the gastrointestinal system. We studied the pathogenesis of GIST by measurement of microvascular density (MVD) and expression of nine signal transduction molecules that have known roles in diverse types of cancers (PI3K, Akt, pTEN, uPA, MMP2, MMP9, HIF1, NOS2, and VEGF) in the tumorous tissues and adjacent normal tissues of 124 GIST patients. We also compared the MVD (a measure of angiogenesis) in tumorous and adjacent normal tissues. Our results indicated significant differences in the expression of the assayed mRNAs and proteins in GIST cells and in adjacent normal cells. In addition, tumorous tissues had significantly higher MVD than adjacent normal tissues. These nine genes have potential for use for diagnosis, outcome prediction, and as new targeted treatments for GISTs. Keywords: gastrointestinal stromal tumors (GISTs), angiogenesis, PI3K/AKt signaling pathway, microvascular density (MVD), endothelial growth factor (VEGF), disease-free survival.

Physical guidance cues have been exploited to stimulate neuron adhesion and neurite outgrowth. In the present study, 3D silk fibroin scaffolds with uniaxial multichannels (diameters of 42-142 μm) were prepared by a directional temperature field freezing technique, followed by lyophillization. By varying the initial silk fibroin concentration the chemical potential and quantity of free water around cylindrical ice crystals could be controlled to control the cross-section morphology of the scaffold channels. Ridges aligned also formed on the inner surface of the mutichannels in parallel to the direction of the channels. In vitro, primary hippocampal neurons were seeded in these 3D silk fibroin scaffolds with uniaxial multichannels with a diameter about 120 μm. The morphology of the neurons was multipolar and alignment along the scaffold channels was observed. Cell-cell networks and cell-matrix interactions established by newly formed axons were observed after 7 days in culture. These neurons expressed β-III-tubulin, nerve filament and microtubule-associated protein, while glial fibrillary acidic protein immunofluorescence was barely above background. The ridges on the inner surface of the channels played a critical role in the adhesion and extension of neurons by providing continuous contact guidance. These new 3D silk scaffolds with uniaxial multichannels provided a favorable microenvironment for the development of hippocampal neurons by guiding axonal elongation and cell migration.

BackgroundGenetic variation influences susceptibility or resistance to tuberculosis (TB). Interleukin-6 contributes to protection against TB in mice, however, its role in regulating susceptibility or resistance to TB in humans is unclear.MethodsGenotyping of polymorphisms in IL-6 and IL-6R (CD126) genes were performed in two independent cohorts, namely experimental (495 cases and 358 controls) and validation (1383 cases and 1149 controls) populations. The associations of the variants with tuberculosis were tested using two case-control association studies. In addition, the regulatory effects of SNP rs1800796 (-572C>G) on IL-6 production in plasma and CD14(+) monocyte cultures stimulated with a Mycobacterium tuberculosis (Mtb) product were assessed.ResultsThe rs1800796 polymorphism is associated with increased resistance to TB (odds ratio, 0.771; confidential interval 0.684-0.870). The rs1800796GG genotype is strongly associated with reduced risk to TB (odds ratio, 0.621; confidential interval 0.460-0.838). Interestingly, CD14(+) monocytes isolated from individuals with rs1800796GG genotype produced significantly lower IL-6 in response to Mtb 19kDa lipoprotein than those with CC or CG genotype do.ConclusionsWe identified a genetic polymorphism in IL-6 promoter that regulates the cytokine production and host resistance to pulmonary TB in Chinese population.

PurposeTo investigate the prevalence of diabetic retinopathy (DR) and relative risk factors among Chongqing pre-diabetes patients.MethodsA total of 750 participants were recruited in this cross-sectional study. All participants underwent a complete physical examination and an oral glucose-tolerance test. In all, 110 of the 125 newly diagnosed pre-diabetics and their healthy spouses as controls were examined with fluorescence fundus angiographies, and their blood with biochemical analyses. All the pre-diabetics with DR (23 subjects), 23 normal controls and 23 pre-diabetics without DR were compared for serum concentrations of regulated upon activation, normal T-expressed and secreted (RANTES). Student's t-test was used to compare continuous variables, and χ (2) test and analysis of variance to compare proportions among groups. Multiple logistic regression models were used to determine the risk factors for DR in pre-diabetics.ResultsIn all, 20.91% of the 110 pre-diabetics showed mild non-proliferative DR (NPDR). There was a statistically significant difference in serum concentrations of RANTES between pre-diabetics with and without DR (P<0.01), and also between pre-diabetics with DR and normal controls (P<0.01). However, age, body mass index, waist-hip ratio, triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein-C, low-density lipoprotein-C, blood urea nitrogen, blood creatinine, and urine albumin excretion rate seemed to have no reliable relationship with DR in pre-diabetics (P>0.05).ConclusionThe prevalence of DR in Chongqing pre-diabetes patients in the study was about 20.91% and only mild NPDR was found. It seems that RANTES is one possible risk factor associated with DR in pre-diabetics, not age, TG and TC, and others.Eye advance online publication, 23 March 2012; doi:10.1038/eye.2012.50.

Elevated oxidative stress is reported to be associated with pregnancy complications in highly prolific sows. Oxidative DNA damage and the antioxidant status were determined in blood samples collected during the course of gestation and lactation in multiparous sows. Blood samples were drawn from sows (n = 5) on days 30, 60, 90 and 110 of gestation (G30, G60, G90 and G110, respectively), on day 3, 10 and 18 of lactation (L3, L10 and L18, respectively) and on day 5 of postweaning (W5). Lymphocytes were isolated from the fresh blood and cryopreserved in each time point. Lymphocyte DNA damage was analyzed by alkaline single-cell gel electrophoresis (comet assay) to determine the single- and double-strand brakes and endogenous antioxidant concentrations using an HPLC system with UV detection. The comet assay showed elevated (P < 0.05) DNA damage (between 38% and 47%) throughout the gestational and lactational periods than during early gestation (G30; 21%). Plasma retinol concentration was reduced (P < 0.05) at the end of gestation (G110) compared with G30. Plasma α-tocopherol concentrations also showed a similar trend as to retinol. This study indicates that there is an increased systemic oxidative stress during late gestation and lactation, which are not fully recovered until the weaning compared with the G30, and that antioxidant nutrients in circulation substantially reduced in the mother pig at G110.

Catechins containing galloyl moieties are important natural antioxidant compounds. In this paper, we review the multiple mechanisms whereby catechins containing a galloyl moiety can target key proteins to inhibit sexual transmission of HIV-1, as well as HIV-1 fusion, HIV-1 reverse transcriptase, HIV-1 integrase and HIV-1 protease. Furthermore, catechins with a galloyl moiety can mediate host cell factors such as nitric oxide synthase, nuclear factor-κB and casein kinase II to inhibit HIV-1 infection. The most significant inhibitory effect is blocking gp120 binding to isolated human CD4+ T cells. The multiple mechanisms underlying the anti-HIV activity of galloyl-containing catechins predict that these catechins could be used as alternative therapies in the treatment of HIV infection.

BACKGROUND AND PURPOSE Paired-like homeodomain transcription factor 3 (PITX3) is an important transcription factor for differentiation and survival of dopaminergic neurons. Recent reports have shown a strong association of polymorphisms in the PITX3 gene with Parkinson's disease (PD). Our study was designed to verify whether three previous PITX3 SNPs (rs2281983, rs4919621 and rs3758549) were associated with PD in the Chinese population. We also investigate the association of novel polymorphisms in PITX3 gene with PD. METHODS All the polymorphisms of PITX3 we found in this study were sequenced by PCR products from both directions with dye terminator methods using an ABI-3100 sequencer. We included 356 sporadic PD patients and 300 healthy elderly people as controls. RESULTS We provide evidence for strong association of a novel polymorphism c.219G>A (p = 0.000307) with PD. Our data showed that the substitution of c.219G>A in PITX3 Exon 3 was significantly higher in PD compared with control. Previous finding suggesting three SNPs (rs2281983, rs4919621 and rs3758549) in the PITX3 gene to be associated with PD could not be replicated. CONCLUSIONS Our findings indicate that a novel synonymous SNP in PITX3 gene may contribute to PD risk in the Chinese population.