Protective effects of recombinant lactoferrin with different iron saturations on enteritis injury in young mice.

Infant intestinal development is immature and, thus, is vulnerable to bacterial and viral infections, which damage intestinal development and even induce acute enteritis. Numerous studies have investigated that lactoferrin (LF) has protective effects on the intestine and may play a role in preventing intestinal inflammation in infants. Lactoferrin is divided into 2 types, namely apo-LF and holo-LF, depending on the degree of iron saturation, which may affect its bioactivities. However, the role of LF iron saturation in protecting infant intestinal inflammation has not been clearly clarified. Therefore, in this study, young mice models with intestinal damage induced by lipopolysaccharides (LPS) in vivo and primary intestinal epithelial cells in vitro were constructed to enteritis injury in infants for investigation. The apo-LF and holo-LF were subsequently applied to the mouse models to investigate and compare their levels of protection in the intestinal inflammatory injury, as well as to identify which LF was most active. Moreover, the specific mechanism of the LF with optimal iron saturation was further investigated through Western blot assay. Results demonstrated that disease activity index, shortened length of colon tissue, and histopathological score were significantly decreased in the apo-LF group compared with those of the LPS group and the holo-LF group. In the apo-LF group, the concentration of LPS in the intestinal tract and the number of gram-negative bacteria colonies decreased significantly and the expression levels of proinflammatory factors in the colon tissue were downregulated, in comparison with those in the LPS group. The findings of this study thus verify that apo-LF can significantly alleviate enteritis injury caused by LPS, through regulating the PPAR-γ/PFKFB3/NF-κB inflammatory pathway.

[Overview of the role of inhaled corticosteroids in chronic obstructive pulmonary disease from evolution of guidelines].

In the treatment of stable chronic obstructive pulmonary disease (COPD), international guidelines have updated the recommendations for inhaled corticosteroids (ICS) based on the accumulated clinical evidences, and the understanding has gone further from "controversy" to "affirmation" until the presence of the lastest guideline that indicates patients are divided into two phenotypes according to the clinical characteristics of dyspnea and acute exacerbation for adjustments in treatment strategy, and for patients with frequent acute exacerbations during the last one year, combined with their blood eosinophil counts, the individualized treatments including ICS are recommended.

Osteoporosis drugs for prevention of clinical fracture in white postmenopausal women: a network meta-analysis of survival data.

By Bayesian random effects network meta-analysis stratified by prevalent vertebral fracture (PVF), we conclude that different effective drugs should be used to prevent fragility fractures according to postmenopausal women with or without PVF and that there are two drugs (i.e., parathyroid hormone (1-84) and abaloparatide) less tolerated than placebo. INTRODUCTION: No studies have compared various osteoporosis drugs in postmenopausal women (PMW) either with or without prevalent vertebral fracture (PVF). We aimed to compare them in the two different subgroups. METHODS: We searched different databases to select relevant studies. We performed Bayesian random effects network meta-analysis to synthesize hazard ratio (HR) and 95% confidence interval (CI) for clinical fracture stratified by PVF and to synthesize risk ratio (RR) for tolerability and vertebral fracture. RESULTS: We included 33 trials involving 79,144 PMW. In the PVF ≥ 50% subgroup, teriparatide (HR 0.39, 95% CI 0.28-0.57), romosozumab (HR 0.49, 95% CI 0.29-0.75), risedronate (HR 0.62, 95% CI 0.50-0.79), zoledronate (HR 0.67, 95% CI 0.47-0.96), and alendronate (HR 0.69, 95% CI 0.47-0.97) reduced clinical fracture risk. In the other subgroup, abaloparatide (HR 0.56, 95% CI 0.33-0.92), romosozumab (HR 0.67, 95% CI 0.47-0.95), and denosumab (HR 0.68, 95% CI 0.50-0.85) reduced clinical fracture risk. Five drugs reduced vertebral fracture risk in the PVF ≥ 50% subgroup whereas seven did in the other subgroup. All drugs did not increase withdrawal risk except for parathyroid hormone (1-84) (PTH) (RR 1.9, 95% CI 1.4-2.6) and abaloparatide (RR 1.6, 95% CI 1.2-2.3). CONCLUSION: Different effective drugs should be used to prevent fragility fractures according to PMW with or without PVF, and romosozumab is the only one which can reduce clinical and vertebral fractures in both of the two populations. PTH and abaloparatide are less tolerated than placebo whereas the eight other drugs assessed in the study have the same tolerability as placebo.

Expression of Raptor and Rictor and their relationships with angiogenesis in colorectal cancer.

Mammalian target of rapamycin (mTOR) has two subtypes, i.e., mTORC1 and mTORC2, which contain the Raptor and Rictor core molecules, respectively. The effect of Raptor and Rictor on hypoxia inducible factor (HIF)-1α, HIF-2α, and vascular endothelial growth factor (VEGF) in colorectal cancer (CRC) is unclear. In this work, we investigated the correlations among Raptor, Rictor, HIF-1α, HIF-2α, and VEGF expression in CRC. We subsequently analyzed the clinicopathological features of patients. Immunohistochemistry, western blot, and RT-PCR analyses were performed to detect the expression of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF in 120 cases of CRC and 60 cases of normal colorectal mucosa. CD34 was used to label microvascular density (MVD), which was found to be higher in patients with positive Raptor or Rictor than in those with negative Raptor or Rictor. The positive rates of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF in CRC were significantly higher than in normal colorectal mucosa. Raptor expression was positively correlated with HIF-1α and VEGF but not with HIF-2α expression. By contrast, Rictor expression was positively correlated with HIF-2α and VEGF but not with HIF-1α expression. Survival analysis further indicated that Raptor, Rictor, HIF-1α, HIF-2α, VEGF and lymph node metastasis were independent prognostic factors in CRC. To conclude, Raptor and Rictor expression was related to the initiation and development of CRC and angiogenesis in different ways. The combined detection of Raptor and Rictor is important for patients with colorectal carcinoma in prognosis and optimal therapy.

Short communication: Decrease of lipid profiles in cow milk by ultra-high-temperature treatment but not by pasteurization.

Triglyceride (TG) and fatty acid profiles of raw (RM), pasteurized (PM, 85°C for 15 s), and indirect UHT-treated (UM, 135°C for 15 s) cow milk were investigated by a lipidomics approach. Ninety-four TG were identified and all were present at significantly lower concentrations in UM than in RM or PM, and free fatty acid contents were significantly higher in UM than in RM and PM, indicating that TG lipolysis occurred to a greater degree in UM than in RM and PM. In addition, UM contained significantly fewer unsaturated fatty acids (14 types) than those in RM and PM, including C14:1n-5, C15:1n-5, C16:1n-7, C17:1n-7, C18:1n9 cis, C18:2n-6 cis, C18:3n-3, C18:3n-6, C20:1, C20:2, C20:3n-6, C20:3n-3, C20:4n-6, and C20:5n-3. However, we detected no significant differences between RM and PM in these fatty acids. In conclusion, UHT treatment, but not pasteurization, caused loss of the nutritional quality and bioactivity of cow milk lipid profiles.

[Association of plasma roundabout 4 concentration with pulmonary ventilation function decline in COPD patients].

Objective: To investigate the association of plasma roundabout 4 concentration with pulmonary ventilation function decline in chronic obstructive pulmonary disease (COPD) patients. Methods: To get the effective data, the study was conducted in the outpatient department of West China Hospital from September 2017 to September 2018. The subjects meeting the inclusion and exclusion criteria were continuously included. Among them, the COPD group (75 cases) was from the respiratory outpatient department, and the healthy control group (57 cases) was from the health examination center at the same time. Data of basic demographic characteristics, clinical characteristics, pulmonary ventilation function parameters and blood samples were collected. The concentrations of roundabout 4, C reactive protein (CRP), interleukin (IL)-6, IL-8, IL-1b and tumor necrosis factor (TNF)-α in plasma were detected, and the differences among groups were compared, the correlation between plasma roundabout 4 and pulmonary ventilation function parameters and inflammatory factors was analyzed. The diagnostic efficiency of roundabout 4 to COPD was analyzed according to receiver operating characteristic (ROC) curve. Results: The plasma concentration of roundabout 4 in COPD group was significantly higher than that in healthy control group [(41.3±14.2) vs (27.7±13.3) ng/L; P<0.001], the sensitivity and specificity of roundabout 4 in the diagnosis of COPD were 0.827 and 0.702 respectively. Correlation analysis showed that the plasma concentration of roundabout 4 was negatively correlated with lung function parameters forced expiratory volume in one second/forced vital capacity (FEV(1)/FVC), the first second forced expiratory volume as a percentage of the estimated value (FEV(1)%pred), forced exhalation of 50% and 25% lung capacity (MEF50, MEF25) and maximal mid-expiratory flow (MMEF) (r=-0.399, -0.321, -0.439, -0.363, -0.458; all P<0.001), positively correlated with CRP (adjusted r=0.311, P<0.001). Conclusion: The increased concentration of roundabout 4 in plasma leads to the decline of pulmonary ventilation function in COPD patients.

[Effect of cognitive impairment on social function and quality of life in chronic schizophrenia].

Objective: To clarify the effect of cognitive impairment on social function and quality of life of chronic schizophrenia, and provide clinical cognitive strategies for improving the social function and quality of life of patients with schizophrenia. Methods: Atotal of 158 patients with chronic schizophrenia were selected from May 2017 to October 2017 in the Psychiatry Department of the Third Affiliated Hospital of Sun Yat-sen University received psychological assessments, such as, MATRICS Consensus Cognitive Battery(MCCB), the Brief Psychiatric Rating Scale(BPRS), the Personal and Social Performance scale(PSP), and Schizophrenia Quality of Life Scale(SQLS). We further explored the effects of neurocognitive and social cognitive functions on their individual and social performance and quality of life in patients with schizophrenia. Results: (1) The scores of SQLS in the group with impaired social cognitive function were higher than those with good social function(101±46 vs 76±40, P=0.002). (2) The digital sequence and continuous performance test of the socially functional group were higher than the defect group. (3) There was a significant correlation between the years of education(R(2)=0.334, F=25.542), continuous performance (R(2)=0.316, F=35.647), BPRS (R(2)=0.280, F=60.386) and social function (P<0.001). (4) BPRS (R(2)=0.486, F=228.28), and emotional management (MSCEIT) (R(2)=0.510, F=124.789), education (R(2)=0.531, F=90.161), age (R(2)=0.539, F=69.644) significantly affected the SQLS score of patients with schizophrenia(P<0.001). Conclusion: The social function and quality of life of patients with schizophrenia are significantly correlated with their years of education and disease severity. Continuous performance in neurocognition significantly affects the social function of patients with schizophrenia, and emotional management in social cognition significantly affects their quality of life. Socially functional schizophrenia patients have higher digital sequences (working memory) and continuous performance (attention/alertness) scores.

[Bioinformatics analysis of severe emphysema genome microarray based on GEO database].

Objective: To investigate differential genes (DEGs) between no/mild and severe emphysema by bioinformatics analysis. Methods: The microarray dataset GSE1650, of lung tissue in no/mild and severe emphysema, was downloaded from the GEO database, and DEGs were obtained by t test. Analysis of DEGs based on DAVID database was used to obtain gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway. The protein-protein interaction network (PPI) was established using STRING database to identify hub genes. Results: A total of 76 DEGs were obtained, of which 62 genes were up-regulated and 14 genes were down-regulated in severe emphysema group. Gene ontology showed that the DEGs were mainly involved in neutrophil chemotaxis, cellular response to interleukin-1, extracellular matrix organization, immune response, and KEGG pathway involved cytokine-cytokine receptor interaction, ECM-receptor interaction, PI3K-Akt signaling pathway, platelet activation. Seventeen hub genes were recognized by PPI analysis, including CXCL8, RRAD, CLU, TIMP1, SEPP1, ISLR, BGN, COL1A1, COLIA2, ACTA2, ACTN1, FIGF, TPM1, TPM2, LUM, COL6A3 and TAGLN. Among them, fifteen genes (CLU, TIMP1, SEPP1, ISLR, BGN, COLIA2, COL1A1, ACTA2, ACTN1, FIGF, TPM1, TPM2, LUM, COL6A3, TAGLN) were up-regulated and two genes (CXCL8, RRAD) were down-regulated. Conclusion: Bioinformatics analysis based on GEO database showed that there were DEGs between non/mild and severe emphysema patients.

Systemic disruption of the homeostasis of transfer RNA isopentenyltransferase causes growth and development abnormalities in Bombyx mori.

Isopentenylation at A37 (i6 A37) of some transfer RNAs (tRNAs) plays a vital role in regulating the efficiency and fidelity of protein synthesis. However, whether insects, which are well known for their highly efficient protein synthesis machinery, employ this regulatory mechanism remains uninvestigated. In the current study, a candidate tRNA isopentenyltransferase (IPT) gene with three alternative splicing isoforms (BmIPT1-BmIPT3) was identified in Bombyx mori (silkworm). Only BmIPT1 could complement a yeast mutant lacking tRNA IPT. Phylogenetic analysis showed that silkworm tRNA IPT is conserved in the Lepidoptera. BmIPT was expressed in all B. mori tissues and organs that were investigated, but was expressed at a significantly higher level in silk glands of the fourth instar compared to the first day of the fifth instar. Interestingly, BmIPT was expressed at a significantly higher level in the domesticated silkworm, B. mori, than in wild Bombyx mandarina in multiple tissues and organs. Knock-down of BmIPT by RNA interference caused severe abnormalities in silk spinning and metamorphosis. Constitutive overexpression of BmIPT1 using a cytoplasmic actin 4 promoter in B. mori raised its messenger RNA level more than sixfold compared with nontransgenic insects and led to significant decreases in the body weight and cocoon shell ratio. Together, these results confirm the first functional tRNA IPT in insects and show that a suitable expression level of tRNA IPT is vital for silk spinning, normal growth, and metamorphosis. Thus, i6 A modification at position A37 in tRNA probably plays an important role in B. mori protein synthesis.

Determination of sulbactam in raw bovine milk by isotope dilution-ultra-high-performance liquid chromatography-tandem mass spectrometry.

We developed a sensitive and selective isotope dilution ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of sulbactam residue in raw bovine milk. Sulbactam and internal standard, sulbactam-d5, were extracted from raw bovine milk via liquid-liquid extraction and enriched with strong anion exchange solid-phase extraction cartridges and finally analyzed by using UPLC-MS/MS with multiple reaction monitoring mode. The method was validated according to European regulations. The calibration curve showed good linearity, with a correlation coefficient of 0.9998. Decision limit and detection capability of sulbactam were determined by matrix calibration curve and were 0.0445 and 0.0517 µg/L, respectively. The recoveries of sulbactam in fortified raw bovine milk ranged from 72.1 to 91.5%, with the intra- and interday relative standard deviations ranging from 3.0 to 18.9%. Furthermore, the developed method was applied to analyzing real raw bovine milk samples collected from dairy farms in Beijing, China. Sulbactam was not determined in all samples. The proposed method could ultimately serve as a methodological foundation for the determination of sulbactam in different types of raw milk and dairy products.

All-optical multilevel amplitude regeneration in a single nonlinear optical loop mirror.

We experimentally demonstrate all-optical amplitude regeneration of 4-level pulse amplitude modulated signals (PAM4) based on a single nonlinear optical loop mirror (NOLM). Four power-plateau regions are achieved using return-to-zero (RZ) pulses of narrow pulse-width, enabling large nonlinear phase shifts within the highly nonlinear fiber (HNLF). We quantify noise suppression characteristics at each amplitude level and obtain an overall EVM improvement of 0.92dB by optimizing input power and distortion strength. A theoretical analysis has been also carried out matching the experimental results and revealing the design characteristics of the regenerator's nonlinear transfer function.

Overexpression of EPS8L3 promotes cell proliferation by inhibiting the transactivity of FOXO1 in HCC.

The homology of epidermal growth factor receptor pathway substrate 8 (EPS8), EPS8L3, is elevated significantly in hepatocellular carcinoma (HCC) tissues and cell lines compared with the normal liver tissues and cell lines. The MTT and colony formation assays demonstrated that overexpressing EPS8L3 enhances, while silencing reduces the proliferation of HCC cells. Further experiments illustrated that overexpressing EPS8L3 promotes the expression of p-AKT, Cyclin D1, but inhibits the transcriptional activity of FOXO1. Besides, colony formation assay demonstrated that AKT inhibitor suppresses the effect of EPS8L3 on proliferation in EPS8L3-overexpressing cells, whereas AKT restores the proliferation of EPS8L3-silenced cells, suggesting that EPS8L3 might promote proliferation by hyperactivating the AKT signaling pathway and subsequently inhibiting the FOXO1 transcriptional activity. Our results provide new view between EPS8L3 and progression of human HCC, suggesting that EPS8L3 may be a novel therapeutic target for HCC.

A metabolomics approach to characterize raw, pasteurized, and ultra-high temperature milk using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and multivariate data analysis.

We developed a metabolomics workflow using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to determine the effect of thermal treatment on milk composition and metabolites based on multivariate data analysis. We analyzed raw, pasteurized, and UHT milk samples. The samples were first centrifuged to remove the fat layer and mixed with methanol to precipitate proteins. Subsequently, the supernatant was analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in electrospray negative mode. Mass spectral data were acquired in MSE mode, a technique whereby both precursor and fragment mass spectral are simultaneously acquired by alternating between low and high collision energy (CE) during a single analytical run, to enable metabolite identification. Based on multivariate data analysis, these markers were significantly affected by thermal treatment. Among the 8 potential markers, we identified 7 oxylipids (9-hydroxydecanoic acid, 12-hydroxydodecanoic acid, 2-hydroxymyristic acid, 3-hydroxytetradecanoic acid, 5-hydroxyeicosatetraenoic acid, 3-hydroxyhexadecanoic acid, and 10-hydroxyoctadecanoic acid) and 1 phospholipid (LysoPE, hexadecanoyl-lysophosphatidylethanolamine). The oxylipids seemed to be adequate for distinguishing UHT milk from raw and pasteurized milk. The structures of the 8 potential markers were identified and characterized using informatics software. Our metabolomics workflow provides a fast approach for the identification of various types of milk.

[Effect of dopamine on intracerebral glutamate uptake ability in rats with minimal hepatic encephalopathy and the pathogenesis of minimal hepatic encephalopathy].

Objective: To investigate the effect of dopamine (DA) on the glutamate (Glu) uptake ability of neural cells, as well as its effect on cognitive impairment in rats with minimal hepatic encephalopathy (MHE) via related pathways. Methods: A total of 45 Sprague-Dawley rats were randomly divided into control group, MHE model group, and DA intervention model group, with 15 rats in each group. The rats in the MHE model group were given intraperitoneal injection of thioacetamide (TAA), those in DA intervention model group were given intraventricular injection of DA, and those in the control group were given intraperitoneal injection of physiological saline, with a frequency of twice a week for 8 weeks. Cerebral microdialysis was used to measure the change in the content of Glu in the brain in MHE rats and rats with DA intervention; RT-PCR and Western blotting were used to measure the relative mRNA and protein expression of trace amine-associated receptor 1 (TAAR1) and excitatory amino acid transporter 2 (EAAT2); the changes in the expression of EAAT2 and extracellular Glu level were measured after intracerebroventricular injection of TAAR1 siRNA and TAAR1 plasmid in MHE rats and rats with DA intervention. One- way analyses of variance for comparison among different groups were performed, categorical data between groups were compared using nonparametric tests. Results: Compared with the control group, the MHE model group had significant increases in the content of DA in liver tissue, plasma, and brain tissue (4.90 ± 0.13 ng/g vs 1.20 ± 0.13 ng/g, P < 0.05; 16.32 ± 1.01 pmol/ml vs 5.50 ± 0.82 pmol/ml, P < 0.05; 732.45 ± 78.85 ng/g vs 387.00 ± 23.36 ng/g, P < 0.05). There was a significant increase in the extracellular Glu level within 40-120 minutes after intracerebral injection of DA in the DA intervention model group. Compared with the control group, the MHE model group and the DA intervention model group had a significant increase in the relative protein expression of TAAR1 (3.72 ± 0.50/4.18 ± 0.43 vs 0.96 ± 0.40, both P < 0.05) and a significant reduction in the expression of EAAT2 (0.46 ± 0.16/0.51 ± 0.20 vs 0.92 ± 0.11, P = 0.013 and 0.036). Compared with the model group treated with empty vector, the MHE model group and the DA intervention model group had a significant increase in the relative protein expression of EAAT2 after TAAR1 siRNA intervention (0.86±0.142 vs 0.56 ± 0.060, P = 0.028; 0.99 ± 0.056 vs 0.43 ± 0.098, P = 0.0010) and a significant reduction in the extracellular Glu level in the brain at 60-120 minutes after injection, while after TAAR1 plasmid intervention, the MHE model group and the DA intervention model group had a significant reduction in the relative protein expression of EAAT2 (0.20 ± 0.040 vs 0.48 ± 0.08, P = 0.006; 0.24 ± 0.05 vs 0.54 ± 0.07, P = 0.004) and a significant increase in the extracellular Glu level in brain at 60-100 minutes after injection. Conclusion: DA interacts with TAAR1 in brain tissue to induce extracellular accumulation of Glu, thus leading to the disorder of the TAAR1-EAAT2 signaling pathway in brain tissue and ultimately injuring the cognitive function of MHE rats.

The diverse genetic landscape of neurodevelopmental disorders.

Advances in genetic tools and sequencing technology in the past few years have vastly expanded our understanding of the genetics of neurodevelopmental disorders. Recent high-throughput sequencing analyses of structural brain malformations, cognitive and neuropsychiatric disorders, and localized cortical dysplasias have uncovered a diverse genetic landscape beyond classic Mendelian patterns of inheritance. The underlying genetic causes of neurodevelopmental disorders implicate numerous cell biological pathways critical for normal brain development.

Cost-effectiveness analysis of additional docetaxel for metastatic hormone-sensitive prostate cancer treated with androgen-deprivation therapy from a Chinese perspective.

The E3805 (CHAARTED) study found that docetaxel combined with androgen-deprivation therapy (ADT) significantly improved overall survival of patients with metastatic hormone-sensitive prostate cancer. This study aims to determine whether docetaxel combined with ADT is a cost-effective strategy for advanced prostate cancer in China. According to the E3805 study, two groups (docetaxel + ADT and ADT alone) and three health states [progression-free survival (PFS), progressive disease (PD) and death] were analysed in a Markov model. All medical costs were calculated from the Chinese societal perspective. Quality-adjusted life year (QALY) and incremental cost-effectiveness ratios (ICERs) were applied as the primary outcome. Overall, the addition of docetaxel was estimated to increase the cost by $12 816.93, with a gain of 0.48 QALY. Additionally, for patients with high-volume disease, the increased cost and effectiveness were $14 627.75 and 0.69 QALYs in docetaxel + ADT group versus the ADT alone group, and the ICER was $21 199.63 per QALY. These ICERs are far more than the commonly accepted willingness-to-pay (WTP) threshold of $20 301 per QALY in China. In spite of longer survival time, docetaxel combined with ADT is not a recommended cost-effective treatment for metastatic hormone-sensitive prostate cancer in the Chinese setting.

[Prevalence and clinical characteristics of blood eosinophilia in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To investigate the prevalence and clinical characteristics of peripheral blood eosinophilia (EOS) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: From July 2014 to June 2016, AECOPD patients in the Department of Respiratory Medicine of Affiliated Hospital of Chengdu University, were retrospectively stratified into two groups according to two standards of eosinophilic exacerbations (the peripheral blood eosinophil count ≥2% or ≥3% on admission). Demography, clinical symptoms, laboratory results, length of stay, total hospitalization expenses, and defined daily expenses were compared between groups. Results: A total of 559 cases with AECOPD were finally recorded, the prevalence of eosinophilia was 43.1% (241 cases by EOS≥2%) and 27.2% (152 cases by EOS≥3%), respectively. According to either standard, there were no significant differences in sexes, age, course of disease (P>0.05), and there were no significant differences in global initiative for chronic obstructive lung disease (GOLD) grades, parameters of pulmonary function, modified british medical research council (mMRC) scores, rate of antibiotic use, systemic glucocorticoids administration, and average daily expenses (P>0.05). According to 2% standard, leucocytes, neutrophils, monocytes, hs-CRP were lower than non-eosinophilic patients [(5.9±2.0)×10(9)/L vs (8.2±4.0)×10(9)/L, (3.9±1.6)×10(9)/L vs (6.5±3.8)×10(9)/L, (0.446±0.169)×10(9)/L vs (0.501±0.276)×10(9)/L, (25.8±35.9) vs (46.2±55.6) mg/L, all P<0.01]; basophils, lymphocytes were higher than non-eosinophilic patients [(0.043±0.025)×10(9)/L vs (0.029±0.021) ×10(9)/L, (1.3±0.6) ×10(9)/L vs (1.1±0.6) ×10(9)/L, both P<0.01]; length of stay, total hospital expense were shorter (or lower) than non-eosinophilic patients [(10.6±5.0) vs (11.6±5.8) d, (11 851±7 491) vs (14 254±10 751) RMB, both P<0.05]. According to 3% standard, leucocytes, neutrophils, monocytes, hs-CRP were lower than non-eosinophilic patients (all P<0.05), and basophil were higher than non-eosinophilic patients (P<0.01), but no significant differences were observed in lymphocytes, length of stay and total hospital expense (all P>0.05). Conclusion: Eosinophilia is of relative high prevalence in AECOPD patients, and basophil in eosinophilic patients is higher than non-eosinophilic patients.

RESISTIN INHIBITS GLUCOSE-STIMULATED INSULIN SECRETION THROUGH MIR-494 BY TARGET ON STXBP5.

AIMS: Resistin has been reported to impair the pancreatic beta cells and associated with insulin resistance. MicroRNAs (miRNAs) are short, endogenously produced non-coding ribonucleotides that bind mRNAs and function mainly as negative regulators in mammals. MiRNAs have been implicated in many diseases, including insulin resistance and diabetes. A considerable body of evidence has indicated an important function for miRNAs in insulin secretion. The current study was designed to investigate the effects of miR-494 in the reductions in insulin secretion attributable to resistin. METHODS: Insulin secretion was determined by ELISA, and expressions of genes were identified using quantitative RT-PCR (qRT-PCR) or Western blot analysis. RESULTS: Insulin secretion was significantly reduced by resistin. Overexpression of miR-494 inhibited insulin secretion both in diet culture and high glucose medium in MIN6 cell lines. MiR-494 down-regulated the protein level of STXBP5 by pairing with sites in the 3'UTR. CONCLUSION: miR-494 is involved in the insulin secretion regulated by resistin via its effects on STXBP5 in MIN6 cells.

TALEN-mediated enhancer knockout influences TNFAIP3 gene expression and mimics a molecular phenotype associated with systemic lupus erythematosus.

Linkage disequilibrium poses a major challenge to the functional characterization of specific disease-associated susceptibility variants. Precision genome-editing technologies have provided new opportunities to address this challenge. As proof of concept, we employed TALEN (transcription activation-like effector nuclease)-mediated genome editing to specifically disrupt the TT>A enhancer region to mimic candidate causal variants identified in the systemic lupus erythematosus-associated susceptibility gene, tumor necrosis factor-α-induced protein 3 (TNFAIP3), in an isogenic HEK293T cell line devoid of other linkage disequilibrium-associated variants. Targeted disruption of the TT>A enhancer impaired its interaction with the TNFAIP3 promoter by long-range DNA looping, thereby reducing TNFAIP3 gene expression. Loss of TNFAIP3 mRNA and its encoded protein, A20, impaired tumor necrosis factor-α-induced receptor-mediated downregulation of nuclear factor-κB signaling, a hallmark of autoimmunity. Results demonstrate that the TT>A enhancer variants contribute to causality and function independently of other variants to disrupt TNFAIP3 expression. Furthermore, we believe this approach can be implemented to independently examine other candidate casual variants in the future.

[Morphological analysis of roots and alveolar bone changes after upper anterior retraction with maximum anchorage based on cone-beam computed tomography].

OBJECTIVE: To investigate the remodeling of alveolar bone and the changes of roots after anterior retraction with maximum anchorage by analyzing CBCT data from adult cases. METHODS: The sample comprised 48 incisors and 24 canines from 12 patients (18 to 40 years of age) with problems of maxillary protrusion or upper arch protrusion. CBCT scans were exposed before and after treatment, and lateral cephalometric images as well as multiple planar reconstruction images were reconstructed. Tracing superimpositions of sagittal sections and three-dimensional reconstructions were done for qualitative analysis. For all maxillary anterior teeth, changes of root length, alveolar bone height and labial-palatal thicknesses at different levels were evaluated. The average of measurements taken by the same tester in three times was processed by SPSS 17.0 statistical package. RESULTS: In 6 of the 12 cases, alveolar thickness became thinner on labial side [apical area: (-0.64±1.18) mm] while thicker on palatal side [apical area: (0.93±2.0) mm] and the root length decreased[(-0.95±0.79) mm]. In the other 6 cases, the incisors' alveolar bone became thicker on labial side [apical area: (2.12±1.46) mm] while thinner on palatal side [apical area: (-2.88±0.58) mm]and the loss of root length was obvious[(-2.12±1.43) mm]. In all the 12 cases, the canines' alveolar bone became thinner on labial side especially on the apical level[(-0.27±1.86) mm] while greatly thicker on palatal side [apical area: (6.40±6.00) mm]and the root resorption was slight [(-1.12±1.19) mm]. For all the anterior teeth, the height of alveolar bone reduced around them after retraction. CONCLUSION: When the root apical moved more palatally, more root resorption would occur and the alveolar bone would get thicker on labial side but thinner on palatal side and thinner as a whole after anterior retraction with maximum anchorage.In the vertical direction, the height of the alveolar bone generally decreased on all sides and decreased the most on the palatal side.