Therapeutic effect of the sulforaphane derivative JY4 on ulcerative colitis through the NF-κB-p65 pathway.

The efficacy of the sulforaphane derivative JY4 was evaluated in acute and chronic mouse models of ulcerative colitis induced by dextran sodium sulfate. Oral administration of JY4 led to significant improvements in symptoms, with recovery of body weight and colorectal length, together with reduced diarrhoea, bloody stools, ulceration of colonic tissue and infiltration of inflammatory cells. The oral bioavailability of JY4, determined by comparing oral dosing with injection into the tail vein, was 5.67%, which was comply with the idea in the intestinal function. Using a dual-luciferase reporter assay, immunofluorescence studies, western blot analysis and immunohistochemical staining, JY4 was shown to significant interfere with the NF-κB-p65 signaling pathway. By preventing the activation of NF-κB-p65, JY4 inhibited the overexpression of downstream inflammatory factors, thereby exerting an anti-inflammatory effect on the intestinal tract. This study thus provides a promising candidate drug, and a new concept for the treatment of ulcerative colitis.

Association Between the Lipid Profile and Renal Dysfunction in the Heart Failure Patients.

BACKGROUND/AIMS: In heart failure patients with high prevalence of chronic renal disease (CKD), hospitalization and mortality, whether the lipid profile was associated with renal dysfunction remained unknown. The present study intended to clarify the association between the lipid profile and renal dysfunction in the heart failure patients. METHODS: 336 hospitalized heart failure patients with left ventricle ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. The estimated glomerular filtration rate (eGFR) < 90 mL/min·1.73 m2 was defined as renal dysfunction. The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with eGFR. The significantly correlated factors were enrolled in Logistic regression as confounding factors to determine the association between the lipid profile and renal dysfunction in the heart failure patients. RESULTS: 182 patients (54.2%) had renal dysfunction and 154 patients (45.8%) did not have renal dysfunction. The waist circumference, platelet counts, platelet distribution width (PDW), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (apoA1), albumin and left ventricular ejection fraction (LVEF) are positively correlated with eGFR (all P< 0.05). Meanwhile, the age, mean platelet volume (MPV), neutrophilic granulocyte percentage (NEUT%), urea nitrogen (BUN), creatinine and total bilirubin (TBIL) are negatively correlated with eGFR (all P< 0.05). The total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) show no correlation with eGFR. After the adjustment of sex, hypertension, diabetes mellitus, age, waist circumference, platelet counts, MPV, PDW, NEUT%, TBIL, albumin and LVEF, HDL-C is the only lipid factor still significantly associated with renal dysfunction in hospitalized heart failure patients (OR=0.119, P=0.003). CONCLUSION: Among the lipid profile of TC, triglyceride, LDL-C, HDL-C, apo A1 and apo B, the HDL-C is the only lipid factor significantly associated with renal dysfunction in hospitalized heart failure patients.

Design and synthesis of novel dasatinib derivatives as inhibitors of leukemia stem cells.

We used the concept of bioisosteres to design and synthesize a novel series of dasatinib derivatives for the treatment of leukemia. Unfortunately, most of the dasatinib derivatives did not show appreciable inhibition against leukemia cell lines K562 and HL60. However, acrylamide compound 2c had comparable inhibitory activity with dasatinib against K562 cells (IC50 = 0.039 nM vs. 0.069 nM). And amide compound 2a and acrylamide compound 2c also had comparable inhibitory activity with dasatinib against the leukemia cell line HL60 (IC50 = 0.25 nM and 0.26 nM vs. 0.11 nM). Against the leukemia progenitor cell line KG1a, triazole compounds 15a and 15d-15f and oxadiazole compounds 24a-24d were more potent than dasatinib. In particular, the hydroxyl compounds 15a and 24a were about 64 and 180 fold more potent than dasatinib against KG1a cells (IC50 = 0.14 µM and 0.05 µM vs. 8.98 µM). Compounds 15a and 24a also inhibited colony formation in MCF-7 cells and inhibited cell migration in the cell wound scratch assay in B16BL6 cells. Moreover, hydroxyl compounds 15a and 24a had low toxicity in vivo.

An analysis and prediction of nucleosome positioning based on information content.

Nucleosome positioning plays a key role in the regulation of many biological processes. In this study, the statistical difference of information content was investigated in nucleosome and linker DNA regions across eukaryotic organisms. By analyzing the information redundancy, D k , in Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans genomes, the short-range dominance of nucleotide correlation in nucleosome and linker DNA regions was confirmed. Significant difference of the D k value between the nucleosome and linker DNA regions was also found. The underlying reason for many successful oligonucleotide-based predictions of nucleosome positioning in eukaryotic model organisms may be attributed to the short-range dominance of nucleotide correlation in the nucleosome and linker DNA regions. When applying power spectrum analysis to the nucleosome and linker DNA regions, some obvious differences in sequence periodic signals were observed. The parameter F k was introduced to describe particular base correlation. Furthermore, the support vector machine combining F k was used to classify nucleosome and linker DNA regions in Homo sapiens, Oryzias latipes, C. elegans, Candida albicans, and S. cerevisiae. Independent test demonstrated that a good performance can be achieved by using this algorithm. This result further revealed that base correlation information has an important role in nucleosome positioning.

Flavonoids from Scutellaria amoena C. H. Wright alleviate mitochondrial dysfunction and regulate oxidative stress via Keap1/Nrf2/HO-1 axis in rats with high-fat diet-induced nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is among the most common liver diseases in the world. Flavonoids from Scutellaria amoena (SAF) are used in the treatment of hepatopathy in China. However, the effect and mechanism against NASH remain unclear. We investigated the alleviating effect of SAF on NASH via regulating mitochondrial dysfunction and oxidative stress. METHODS: The effects of SAF on NASH were evaluated using in vitro and in vivo methods. L02 cells were induced by fat emulsion to establish an adipocytes model, followed by treatment with SAF for 24 h. NASH rat models were established by the administration of a high-fat diet for 12 weeks and were administered SAF for six weeks. Changes in body weight, organ indexes, lipid levels, inflammatory cytokines, mitochondrial indicators, and fatty acid metabolism were investigated. RESULTS: SAF significantly improved body weight, organ indexes, lipid levels, liver injury, and inflammatory infiltration in NASH rats. SAF notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Additionally, SAF improved mitochondrial dysfunction, increased the levels of GSH, SOD, ATP synthase, complex I and II, and decreased the level of MDA in liver mitochondria. SAF regulated the expression of ß-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and PPARα. CONCLUSION: SAF can alleviate NASH by regulating mitochondrial function and oxidative stress via the Keap1/Nrf2/HO-1 axis.

The alleviating effect of Scutellaria amoena extract on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NLRP3/ASC/caspase-1 axis.

Background: Scutellaria amoena (SA) is the root of S. amoena C.H. Wright of Labiatae, also known as Scutellaria southwestern. This is mainly distributed in Sichuan, Yunnan, and Guizhou in China. In southwest China, SA is used as an alternative method to genuine medicine for the treatment of allergy, diarrhea, inflammation, hepatitis, and bronchitis. Thus far, studies on the effects of SA on non-alcoholic steatohepatitis (NASH) are lacking. This paper investigated the effect of SA on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NOD-like receptor 3 (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis. Methods: A NASH rat model was induced by a high-fat diet (HFD) for 12 weeks, and rats were orally given different doses of SA extracts (150 and 300 mg/kg/d) for 6 weeks. Changes in histological parameters, body weight, organ indexes, cytokines, and biochemical parameters related to NLRP3 in NASH rats were checked. 16S rRNA gene sequencing and UPLC-MS/MS technology were used to analyze the changes in the gut microbiota composition and its metabolites in NASH rats. Results: SA significantly inhibited the HFD-induced increase in body weight, lipid levels, and inflammatory infiltration. SA notably inhibited the HFD-induced increase in the upper and lower factors of NLRP3, such as transforming growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, pro-IL-18, IL-1ß, pro-IL-1ß, NLRP3, ASC, and caspase-1. Additionally, mRNA expressions of caspase-1, NLRP3, and ASC were significantly downregulated after SA treatment. The results of the intestinal flora showed that SA could increase the diversity of flora and change its structure and composition in NASH rats by reducing Firmicutes/Bacteroidetes (F/B) ratio, Blautia (genus), Lachospiraceae (family), and Christensenellaceae R-7 group (genus), and increasing Muribaculaceae (family) and Bacteroides (genus). The metabolomics revealed that 24 metabolites were possibly the key metabolites for SA to regulate the metabolic balance of NASH rats, including chenodeoxycholic acid, xanthine, and 9-OxoODE. Nine metabolic pathways were identified, including primary bile acid biosynthesis, bile secretion, purine metabolism, and secondary bile acid biosynthesis. Conclusion: SA can regulate the intestinal microbial balance and metabolic disorder by inhibiting the NLRP3/ASC/caspase-1 axis to relieve NASH.

Effects of Tylophora yunnanensis Schltr on regulating the gut microbiota and its metabolites in non-alcoholic steatohepatitis rats by inhibiting the activation of NOD-like receptor protein 3.

ETHNOPHARMACOLOGICAL RELEVANCE: Tylophora yunnanensis Schltr (TYS) is widely distributed in Yunnan, Guizhou, and other places in China. It is commonly used by folks to treat hepatitis and other liver-related diseases; however, its mechanism of action is still unclear. AIM OF THE STUDY: This study aimed to determine the effects of TYS on regulating gut microbiota and its metabolites in non-alcoholic steatohepatitis (NASH) rats by inhibiting the activation of NOD-like receptor protein3 (NLRP3). MATERIAL AND METHODS: An HFD-induced rat model was established to investigate if the intragastric administration of TYS could mediate gut microbiota and their metabolites to ultimately improve the symptoms of NASH. The improving effects of TYS on NASH rats were assessed by measuring their body weight, lipid levels, histopathology, and inflammatory factor levels in the rat models. The regulatory effects of TYS on NLRP3 in the NASH rats were analyzed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), which determined the levels of NLRP3-related factors. The changes in the composition of the gut microbiota of NASH rats were analyzed using 16S rRNA gene sequencing technology. Meanwhile, the Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for the non-targeted analysis of metabolites in the cecum contents. RESULTS: The results showed that TYS could improve NASH by decreasing the body weight and levels of lipid, AST, ALT, LPS, FFA, VLDL, IL-1ß, IL-6, TNF-α, TGF-ß, NLRP3, ASC, and Caspase-1 in the NASH rats. The analysis of gut microbiota showed that TYS could improve the diversity and abundance of gut microbiota and alter their composition by decreasing the Firmicutes/Bacteroidetes (F/B) ratio and relative abundances of Lachnospiraceae, Christensenellaceae, Blautia, etc. while increasing those of Muribaculaceae, Rumiaococcus, Ruminococcaceae, etc. The analysis of metabolites in the cecum contents suggested that the arachidonic acid metabolism, bile secretion, serotonergic synapse, Fc epsilon RI signaling pathway, etc. were regulated by TYS. The metabolites enriched in these pathways mainly included chenodeoxycholic acid, prostaglandin D2, TXB2, 9-OxoODE, and 13(S)-HOTrE. CONCLUSIONS: These findings suggested that TYS could alleviate the NASH symptoms by decreasing the body weight, regulating the lipid levels, reducing the inflammatory response, and inhibiting the expression levels of NLRP3, ASC, and Caspase-1 in the NASH rats. The changes in the composition of gut microbiota and their metabolic disorder were closely related to the activation of NLRP3. TYS could significantly inhibit the activation of NLRP3 and regulate the composition of gut microbiota and the disorder of metabolites during NASH modeling.

Metabolomic analysis of the toxic effect of chronic low-dose exposure to acephate on rats using ultra-performance liquid chromatography/mass spectrometry.

To study the toxic effect of chronic exposure to acephate at low-dose levels, a metabolomics approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) was applied. Three different doses of 0.5 mg/kg/day, 1.5 mg/kg/day, and 4.5 mg/kg/day acephate were administered to Wistar rats for 24 weeks. Endogenous metabolite profiles were obtained with UPLC-MS for all rats at six time points after treatment. Some metabolites like dimethylthiophosphate and uric acid in urine were detected at week 4. Dimethylthiophosphate, which had the most significant elevations compared with other biomarkers, was considered as an early, sensitive biomarker of exposure to acephate. Moreover, there were some endogenous metabolite changes, which demonstrated that the doses of 1.5 mg/kg/day and 4.5 mg/kg/day of acephate led to renal injury and perturbed the normal metabolic processes of rats, including glucose, nucleic acid, and protein metabolism. A connection between exposure to acephate and the metabolic disturbance has been found and interpreted. Our study indicates that the metabolomics approach based on UPLC-MS of urine provides more information on toxicity than the conventional toxicological evaluation methods in measuring changes and can be considered as a promising technique for the study of the toxic effect of acephate.

[Epigenetics in tumorigenesis: advances and clinical implications].

Cancer is a leading cause of death worldwide and the total number of cases globally keeps increasing. For many years, cancer has been thought to be caused by a series of DNA sequence alterations and thus is thought to be a "genetic" disease. However, studies in the last decade, including the large-scale cancer genomics projects, have highlighted the rising importance of epigenetic regulation in cancer. Here, we review recent advances in understanding how chromatin-based epigenetic regulation participates in tumorigenesis and discuss the growing implications of these advances for developing novel strategies to prevent, diagnose, as well as treat cancer.

Synthesis of ponatinib analogues as novel inhibitors of leukemia stem cells.

Aim: To synthesize new analogues of ponatinib and evaluate anti-leukemia cells and cytotoxicity. Methodology & results: The inhibitory activity of compounds 13a and 13c against K562 and HL60 cells was comparable to that of ponatinib (IC50 = 0.74, 0.88 vs 0.64 nM and 0.59, 0.77 vs 0.39 nM, respectively). Compounds 13a and 40b were 34- and 77-fold more potent than ponatinib against KG1a cells (IC50 = 0.091 and 0040 vs 3.6 µM, respectively). Compounds 13a, 13c and 40b also decreased the Abl protein level in the K562 cells, inhibited colony formation in MCF-7 cells and inhibited cell migration in B16BL6 cells. Compound 13a showed low cytotoxicity in 293 cells. Conclusion: Compound 13a was the best lead compound.

Knowledge, attitude, and practice of medication among Haikou residents.

BACKGROUND: Our study aims to explore the knowledge, attitude, and practice (KAP) and its influencing factors of medication among residents in Haikou, the capital city of Hainan Province, and inform the development of interventions to reduce residents' medication errors. METHODS: A cross-sectional questionnaire survey was conducted to investigate the KAP of medication among Haikou residents and its influencing factors from March to September 2019. RESULTS: A total of 471 valid questionnaires were collected (245 online and 226 offline), with an effective recovery rate of 94.2%. The average score of KAP of medication were 52.2±13.08, 27.34±8.14, and 51.54±9.22, respectively. The knowledge score reached "good" in the evaluation criteria of the questionnaire, and the attitude and practice scores were "fair". Multiple linear regression analysis revealed the medication knowledge increased with age; a lower education degree was associated with less knowledge and more medication errors, and a higher education level was associated with more access to medication knowledge. CONCLUSIONS: Education on rational drug use should be performed via multiple ways to promote rational drug use and reduce risky medication behaviors, particularly among residents with low education degrees, e.g., drug counseling and guidance, regularly push medication science popularization, public welfare lecture on rational drug use, organize and compile popular science books.

[Effects of supplement of thyroxine for hypothyroid pregnant rat on the expression of homeobox gene Nkx2.1 mRNA in the offspring's cerebrum tissue].

OBJECTIVE: To explore the effects of thyroid hormone on the expression of homeobox gene Nkx2.1 mRNA in child rat by supplying their hypothyroidism pregnant mother with different dose of levothyroxine (L-thyroxine, L-T(4)) in different times. METHODS: 120 female Wistar rats were randomly divided into eight groups according to the body weight: control group, non-treatment hypothyroidism group, hypothyroidism groups supplied with L-T(4) in high, medium and low dosage in early stage (1st-17th day of pregnancy) and in late stage (18th day of pregnancy-20th day after childbirth). According to 100 grams of body weight, the concentrations of L-T(4) were 3.5, 2.0, 0.5 µg/d in high, medium and low dosage group. All the rats were fed with low-iodine food. The control group was given 200 µg/L potassium iodate solution as drinking water and the other groups were given deionized water. After three months, the rats were mated with normal male rats. After the pregnancy was confirmed, hypothyroidism groups were supplied with L-T(4) of different concentrations. Brain samples were taken from the 17-day fetal rats, new-born and 20-day old offsprings and the levels of Nkx2.1 mRNA in brain tissue were analyzed by real-time fluorescence quantitative PCR techniques. RESULTS: The levels of TT(3) in hypothyroidism groups supplied with L-T(4) in high, medium and low dosages in early and late pregnant stages, non-treatment hypothyroidism group and control group were (0.85 ± 0.17), (0.81 ± 0.18), (0.86 ± 0.21), (0.85 ± 0.20), (0.89 ± 0.18), (0.85 ± 0.20), (0.86 ± 0.20), (1.08 ± 0.07) nmol/L (F = 4.08, P < 0.01); the levels of TT(4) in each group were (0.43 ± 0.16), (0.39 ± 0.11), (0.39 ± 0.13), (0.43 ± 0.17), (0.51 ± 0.19), (0.43 ± 0.16), (0.41 ± 0.15), (39.43 ± 14.16) nmol/L (F = 31.99, P < 0.01); the levels of FT(3) in each group were (3.29 ± 0.61), (3.29 ± 0.61), (3.24 ± 0.61), (3.28 ± 0.63), (3.31 ± 0.59), (3.28 ± 0.50), (3.24 ± 0.49), (4.93 ± 0.46) pmol/L (F = 5.79, P < 0.01); the levels of FT(4) in each group were (3.38 ± 0.80), (3.31 ± 0.67), (3.29 ± 0.73), (3.27 ± 0.71), (3.48 ± 0.81), (3.56 ± 0.66), (3.29 ± 0.61), (27.29 ± 4.53) pmol/L (F = 26.34, P < 0.01). The expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (9.15 × 10(-5) ± 9.17 × 10(-5)) was lower than control group (65.1 × 10(-5) ± 40.90 × 10(-5)) in 17th day of pregnancy (t = 66.224, P < 0.05); the expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (3.16 × 10(-5) ± 0.142 × 10(-5)) was lower than control group (55.6 × 10(-5) ± 51.05 × 10(-5)) in new-born (t = 102.225, P < 0.05); the expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (8.09 × 10(-5) ± 8.21 × 10(-5)) was lower than control group (13.9 × 10(-5) ± 7.43 × 10(-5)) in 20th day after birth (t = 9.235, P < 0.05). The trend of Nkx2.1 mRNA in hypothyroidism groups was decreased in group supplied with L-T(4) in medium dosage in early stage descends in 17th day of pregnancy, new-born and 20th day after birth (57.1 × 10(-5) ± 22.90 × 10(-5)), (30.8 × 10(-5) ± 27.20 × 10(-5)), (17.1 × 10(-5) ± 0.623 × 10(-5)) (F = 13.394, P < 0.01). The expression of Nkx2.1 mRNA in hypothyroidism groups supplied with L-T(4) in medium dosage in early stage in 17th day of pregnancy, new-born and 20th day after childbirth was closest to the control group in every period (t values were 0.225, 0.336, 0.345, all P values > 0.05). CONCLUSION: The difference in the expression of homeobox gene Nkx2.1 mRNA is highly related to the level of thyroid hormone.

Analysis of the rates of emulsification in intraocular silicone oil tamponades of differing viscosities.

AIM: To investigate the rates of emulsification in silicone oil (SO) tamponades of differing viscosities used during pars plana vitrectomy (PPV) in the treatment of complicated vitreoretinal diseases. METHODS: This study was a prospective randomized clinical trial. Totally 290 cases with greater likelihoods of secondary detachment were included and randomly grouped into either Siluron 2000 (n=143) or Siluron 5000 (n=147) SO tamponades with 23-gauge PPV. Patient follow-ups and data analyses were conducted 1, 3, 6, and 12mo post-surgery. RESULTS: The time of the SO emulsification ranged from 1 to 17mo, with a mean of 7.3±4.2mo. The Siluron 5000 group showed a slower emulsification rate in comparison to the Siluron 2000 group. The Siluron 2000 group took a shorter time to show signs of emulsification, necessitating earlier SO removal. However, there were no significant differences in the occurrence of complications, including secondary retinal detachment, cataract, corneal abnormality, high intraocular pressure and hypotony. CONCLUSION: The Siluron 2000 SO tamponade shows a faster rate of emulsification than the Siluron 5000 SO, necessitating earlier removal. Both groups show similar results in terms of anatomical success and visual acuity outcome, and there is no significant difference between the SOs regarding the occurrence of complications.

[Modification and Performance Tests of Visibility Parameterizations for Haze Days].

In order to select a visibility parameterization scheme that can be applied well to the Beijing-Tianjin-Hebei (BTH) region and provide better forecasting, a modified parameterization of visibility based on the aerosol volume concentration and RH is developed in this study. This upgraded parameterization scheme (S1) and other schemes based on PM2.5 and RH (S2) and Mie theory (S3) are evaluated using forecast data from Rapid refresh Multi-scale Analysis & Prediction System-CHEM (RMAPS-CHEM v1.0). A performance test using data from February 2017 showed that:① The concentration of PM2.5 is forecast well in the BTH region. The correlation coefficients of the observed and forecast daily average PM2.5 in most areas are higher than 0.8, and the forecasted values are close to those observed. The mean errors (ME) are -7.54, -0.46, and -11.0µg·m-3 for the forecast domain, south and north of Hebei province, and 12.04, 2.02, and -13.31 µg·m-3 for the cities of Beijing, Tianjin, and Shijiazhuang, respectively. The correlation coefficients for the forecast and observed hourly relative humidity in the three typical cities are above 0.78, and the mean errors are lower than 3.91%. ② All three parameterization schemes predict the time evaluation of visibility in the BTH region during February 2017 well. In general, the visibility predicted with S1 is the lowest, while that of S3 is the highest; the predictions of S2 are intermediate. In most areas of the BTH region, S1 has the minimum root mean squared error (RMSE) and normalized mean error (NME) between the observed and forecast visibility, while S3 has the maximum RMSE and NME. The error of S2 is between that of S1 and S3, but it shows the best performance in the Beijing area. ③ When the observed visibility is higher than 10 km, the predicted visibilities of the three schemes are all lower than the observed visibility, and S3 has the lowest mean error (ME) and RMSE. S1 has the lowest MB, RMSE, and NME when the visibility is lower than 10 km, especially for visibilities of 1 km to 5 km, which occurred more frequently during heavy haze episodes. The comparison of the results indicated that S1 is best for application to haze forecasting in the BTH region.

Influence of Contact Stress on Surface Microstructure and Wear Property of D2/U71Mn Wheel-Rail Material.

To investigate the relationship between surface microstructure and wear mechanism in D2/U71Mn wheel-rail material under different contact stress conditions, rolling wear tests using a GPM-40 wear machine to simulate the wheel-rail operation was performed. After wear tests, an optical microscope (OM), scanning electron microscope (SEM) and micro-hardness testers were used to characterize the microstructure and fatigue wear cracks. The results show that the thickness of the plastic deformation layer and surface hardness is increased with the increase of contact stress. Under high contact stress condition (1200 MPa), the severe plastic deformation layer led to the formation of fatigue wear of wheel-rail samples. Under a contact stress of 700 MPa, the wear mechanism of samples is adhesive wear and wear rate is low. With the increase of contact stress, the fatigue cracks are gradually severe. Under a contact stress of 1200 MPa, the wear mechanism of samples becomes fatigue wear and the fatigue wear cracks cause the increase of wear rate. The fatigue wear can accelerate the wear failure of wheel-rail samples. The fatigue wear cracks of wheel samples are severer than that of rail samples due to both the rate of plastic strain and the content of proeutectoid ferrite.

Impact of individualized active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.

Purpose: Active surveillance of carbapenem-resistant Enterobacteriaceae (CRE) may contribute to the decline of the infection rate. Individualized active surveillance of CRE could cost less than screening all patients. However, the impact of individualized active surveillance on the CRE infection rate in intensive care units (ICUs) has not been well described. Patients and methods: We retrospectively studied the clinical data of all patients admitted in the ICUs of a tertiary-care hospital in China from 2015 to 2017 during two periods, before and after the implementation of individualized active surveillance. During period 1 (January 2015-April 2016), no screening protocol was used. During period 2 (May 2016-December 2017), we implemented active CRE screening for selected patients according to their clinical characteristics. The trend of CRE rate infection was analyzed by a joinpoint regression model, and multivariate analysis was performed to analyze the association of active surveillance, Acute Physiology and Chronic Health Evaluation (APACHE) II score, prior antimicrobial use, length of mechanical ventilation (MV) before infection, and other risk factors with CRE infection rate. Results: A total of 5,372 patients were included. After assessing the patients' clinical characteristics, 72.3% (3,882/5,372) were considered to be at high risk of CRE infection. During period 1, the infection percent of CRE increased by 13.04% every month (95% CI: 5.2-21.5). During period 2, the infection rate decreased (monthly percent change, -3.57%; 95% CI -6.9 to -0.1, P<0.05). Multivariate analysis showed that individualized active surveillance (odds ratio, 0.146; 95% CI, 0.061-0.347; P<0.001) was associated with a reduction of the CRE infection rate, whereas APACHE II score, prior antimicrobial use, and length of MV before infection were independent risk factors. Conclusion: Individualized active surveillance may be associated with a reduction of the overall CRE infection rate in ICUs.

Correlations between the optic nerve head morphology and ocular biometrics in highly myopic eyes.

AIM: To analyze peripapillary atrophy ß/γ zone (PPA-ß/γ) and the optic disc ovality index, and to assess their associations with the axial length (AL), refractive error, best corrected visual acuity (BCVA), choroidal thickness (CT), and age in highly myopic eyes. METHODS: This was a retrospective observational case series. The study included 667 patients consecutively examined for highly myopic eyes [spherical equivalent ≤-6.0 diopters (D) and AL≥26 mm] with or without myopic retinopathy. Each patient went through a comprehensive ophthalmological examination that included spectral domain optical coherence tomography (SD-OCT) of the macula, A-mode ultrasonography, and a cycloplegic refraction test. The ovality index and PPA-ß/γ area were measured from optic disc photographs. RESULTS: A significant association was seen between PPA-ß/γ area and the ovality index (P=0.000, r=-0.232). The PPA-ß/γ area increased significantly with a longer AL, older age, worse BCVA, higher refractive error, and thinner choroid (P<0.01). The oval disc was significantly correlated with a longer AL, older age, worse BCVA, higher refractive error, larger PPA-ß/γ area, and thinner choroid (P<0.01). CONCLUSION: The PPA-ß/γ zone and ovality index in highly myopic eyes show distinct associations with the AL, refractive error, BCVA, age, and CT.

Acute kidney injury is an independent risk factor for myocardial injury after noncardiac surgery in critical patients.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) contributes to mortality and morbidity. However, risk factors accelerating its development remain unclear. The aim of this study was to identify the incidence and risk factors of MINS. METHODS: A retrospective and observational cohort study of critical patients (n=1087) after noncardiac surgery was carried out at a large and tertiary university hospital from January 2012 to January 2013. The clinical data including medical history as well as intraoperative and postoperative variables were recorded. The primary outcome was the occurrence of MINS. Secondary outcomes included 30-day all-cause mortality and the incidence of 30-day major adverse cardiac events (MACE) after surgery. The risk factors of MINS in critical patients were analyzed using logistic regression. RESULTS: MINS had occurred in 188 (17.3%) of the 1087 critical patients. Fifty-seven patients (5.2%) had postoperative acute kidney injury (AKI), wherein stage 1 accounted for 82.5% (47/57), stage 2 accounted for 12.3% (7/57), and stage 3 accounted for 5.3% (3/57). The independent risk factors of MINS in critical patients were emergency surgery (odds ratio [OR], 2.64; 95% confidence interval [CI], 1.60-4.35; P<.001), a longer time of operation (OR, 1.10; 95% CI, 1.03-1.17; P=.004), postoperative AKI (OR, 2.09; 95% CI, 1.15-3.79; P=.015), vasopressor drugs used within 24 hours after operation (OR, 2.27; 95% CI, 1.40-3.67; P=.001), and a higher Acute Physiology and Chronic Health Evaluation II score (OR, 1.05; 95% CI, 1.02-1.08; P=.002). All-cause mortality and MACE after surgery were not related to postoperative AKI (P=.544 for mortality; P=.663 for MACE). CONCLUSIONS: The incidence of MINS in critical patients is high. Postoperative AKI is an independent risk factor of MINS in critical patients. It is recommended that postoperative kidney functions be routinely assessed in all critical patients after noncardiac surgery.

Decreased Diagnostic Accuracy of Multislice Coronary Computed Tomographic Angiography in Women with Atypical Angina Symptoms.

BACKGROUND: Multislice computed tomography (MSCT) coronary angiography (CAG) is a noninvasive technique with a reported high diagnostic accuracy for coronary artery disease (CAD). Women, more frequently than men, are known to develop atypical angina symptoms. The purpose of this study was to investigate whether the diagnostic accuracy of MSCT in women with atypical presentation differs from that in men. METHODS: We enrolled 396 in-hospital patients (141 women and 255 men) with suspected or proven CAD who successively underwent both MSCT and invasive CAG. CAD was defined as any coronary stenosis of ≥50% on conventional invasive CAG, which was used as the reference standard. The patients were divided into typical and atypical groups based on their symptoms of angina pectoris. The diagnostic accuracy of MSCT, including its sensitivity, specificity, negative predictive value, and positive predictive value (PPV), was calculated to determine the usefulness of MSCT in assessing stenoses. The diagnostic performance of MSCT was also assessed by constructing receiver operating characteristic (ROC) curves. RESULTS: The PPV (91% vs. 97%, χ2 = 5.705, P < 0.05) and diagnostic accuracy (87% vs. 93%, χ2 = 5.093,P< 0.05) of MSCT in detecting CAD were lower in women than in men. Atypical presentation was an independent influencing factor on the diagnostic accuracy of MSCT in women (odds ratio = 4.94, 95% confidence intervals: 1.16-20.92, Walds = 4.69, P < 0.05). Compared with those in the atypical group, women with typical angina pectoris had higher PPV (98% vs. 74%, χ2 = 17.283. P < 0.001), diagnostic accuracy (93% vs. 72%, χ2 = 9.571, P < 0.001), and area under the ROC curve (0.91 vs. 0.64, Z = 2.690, P < 0.01) in MSCT diagnosis. CONCLUSIONS: Although MSCT is a reliable diagnostic modality for the exclusion of significant coronary artery stenoses in all patients, gender and atypical symptoms might have some influence on its diagnostic accuracy.

The immunoprotective activity of interleukin-33 in mouse model of cecal ligation and puncture-induced sepsis.

Lymphocyte apoptosis plays a pivotal role in sepsis-induced immunosuppression and is the primary cause of high mortality rates. Interleukin-33 is a member of the interleukin-1 family that is involved in the polarization of T cells toward a T helper 2-cell phenotype and may regulate apoptotic cell death. The objective of the present study was to assess the effects of interleukin-33 on T lymphocyte apoptosis in sepsis and determine the mechanisms involved. Sepsis was induced in C57BL/6 mice via a cecal ligation and puncture. Mice were infused with recombinant interleukin-33 protein at 1h and 6h after surgery. The mortality rates were evaluated over the subsequent 7 days. In a separate experiment, mice were sacrificed 24h after surgery. Bacterial burdens in the blood and peritoneal cavity were calculated to assess the bacterial clearance. Liver, lung and renal pathology were observed via transmission electron microscopy. The serum levels of interleukin-6, interleukin-10, interleukin-17, interferon-γ and tumor necrosis factor-α were measured via enzyme-linked immunosorbent assays. The number of T and B lymphocytes, the percentage of apoptotic cells and the expression of Fas, Bcl-2, caspase-3, caspase-8 and caspase-9 in CD3(+) T lymphocytes were analyzed by flow cytometry. Interleukin-33 enhanced bacterial clearance, attenuated the severity of organ damage and improved the survival of septic mice. Interleukin-33 decreased the levels of interleukin-6, interleukin-10, interferon-γ and tumor necrosis factor-α, and it increased the levels of interleukin-17. Interleukin-33 also inhibited the apoptosis of CD4(+) and CD8(+) T lymphocytes and CD19(+) B cells in the spleen. The number of CD3(+) T cells was higher and the expression of active caspase-3, caspase-8 and caspase-9 was lower in the interleukin-33 group compared to the CLP group. The expression of Fas was lower and the expression of Bcl-2 was higher in the interleukin-33 group than in the CLP group. Interleukin-33 prevented apoptosis of T lymphocytes and improved survival in a mouse model of sepsis.