[Artificial intelligence-assisted identification of mucus plugs in asthma].

Airway mucus plug is an important clinical feature of bronchial asthma and is related to the prognosis of the disease. Clinically, chest CT is a preferred tool for evaluating airway mucus plugs. At present, the interpretation of CT images relies on manual reading, but the airway mucus plugs of patients with bronchial asthma are mostly distributed in the small and medium airways, which are difficult to identify with the naked eye. In recent years, with the continuous progress of deep learning and big data technology, artificial intelligence (AI)-assisted image reading technology has been introduced into clinical application, which has significantly improved the efficiency and accuracy of mucus plug identification. Currently, AI-assisted airway mucus plug identification has been used in respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and bronchial asthma. Therefore, the application of AI counting to mucus plugs in patients with bronchial asthma is of great significance.

[Significance of aspergillus fumigatus-specific IgG in the diagnosis of allergic bronchopulmonary aspergillosis].

The data of 18 patients with allergic bronchopulmonary aspergillosis (ABPA) who received aspergillus fumigatus-specific IgG detection from 2015 to 2021 in Peking University Third Hospital were retrospectively analyzed. Among them, 11 were male and 7 were female, aged 18-79 years. All patients had a history of asthma or symptoms of cough and asthma, and aspergillus fumigatus-specific IgE was positive; 16 patients had total serum IgE>500 U/ml, of which 13 patients had total serum IgE>1 000 U/ml. Among other diagnostic indicators, peripheral blood eosinophils were >0.5×109/L in 16 cases; lung CT showed bronchiectasis in 15 cases; serum aspergillus fumigatus-specific IgG was positive (>120 AU/ml) in 10 cases. There was no significant difference in serum total IgE level, peripheral blood eosinophil count, and bronchiectasis ratio between positive and negative cases of aspergillus fumigatus-specific IgG (all P>0.05). In this study, the positive rate of aspergillus fumigatus-specific IgG in patients with ABPA was more than 50%, which has auxiliary value in the diagnosis of ABPA.

Mating-Type Genes Control Sexual Reproduction, Conidial Germination, and Virulence in Cochliobolus lunatus.

Cochliobolus lunatus (anamorph: Curvularia lunata) is a major pathogenic fungus that causes the Curvularia leaf spot of maize. ClMAT1-1-1 and ClMAT1-2-1, the C. lunatus orthologs of C. heterostrophus ChMAT1-1-1 and ChMAT1-2-1, were investigated in the present study to uncover their functions in C. lunatus. Southern blot analysis showed that these mating-type MAT genes exist in the C. lunatus genome as a single copy. ClMAT1-1-1 and ClMAT1-2-1 were knocked out and complemented to generate ΔClmat1-1-1 and ΔClmat1-2-1 and ΔClmat1-1-1-C and ΔClmat1-2-1-C, respectively. The mutant strains had defective sexual development and failed to produce pseudothecia. There were no significant differences in growth rate or conidia production between the mutant and wild-type strains. However, the aerial mycelia and mycelial dry weight of ΔClmat1-1-1 and ΔClmat1-2-1 were lower than those of wild type, suggesting that MAT genes affect asexual development. ClMAT genes were involved in the responses to cell wall integrity and osmotic adaptation. ΔClmat1-2-1 had a lower conidial germination rate than the wild-type strain CX-3. The virulence of ΔClmat1-2-1 and ΔClmat1-1-1 was also reduced compared with the wild-type. Complementary strains could restore all the phenotypes.

Characterizing diversity in the tumor-immune microenvironment of distinct subclasses of gastroesophageal adenocarcinomas.

BACKGROUND: Gastroesophageal adenocarcinomas (GEAs) are heterogeneous cancers where immune checkpoint inhibitors have robust efficacy in heavily inflamed microsatellite instability (MSI) or Epstein-Barr virus (EBV)-positive subtypes. Immune checkpoint inhibitor responses are markedly lower in diffuse/genome stable (GS) and chromosomal instable (CIN) GEAs. In contrast to EBV and MSI subtypes, the tumor microenvironment of CIN and GS GEAs have not been fully characterized to date, which limits our ability to improve immunotherapeutic strategies. PATIENTS AND METHODS: Here we aimed to identify tumor-immune cell association across GEA subclasses using data from The Cancer Genome Atlas (N = 453 GEAs) and archival GEA resection specimen (N = 71). The Cancer Genome Atlas RNAseq data were used for computational inferences of immune cell subsets, which were correlated to tumor characteristics within and between subtypes. Archival tissues were used for more spatial immune characterization spanning immunohistochemistry and mRNA expression analyses. RESULTS: Our results confirmed substantial heterogeneity in the tumor microenvironment between distinct subtypes. While MSI-high and EBV+ GEAs harbored most intense T cell infiltrates, the GS group showed enrichment of CD4+ T cells, macrophages and B cells and, in ∼50% of cases, evidence for tertiary lymphoid structures. In contrast, CIN cancers possessed CD8+ T cells predominantly at the invasive margin while tumor-associated macrophages showed tumor infiltrating capacity. Relatively T cell-rich 'hot' CIN GEAs were often from Western patients, while immunological 'cold' CIN GEAs showed enrichment of MYC and cell cycle pathways, including amplification of CCNE1. CONCLUSIONS: These results reveal the diversity of immune phenotypes of GEA. Half of GS gastric cancers have tertiary lymphoid structures and are therefore promising candidates for immunotherapy. The majority of CIN GEAs, however, exhibit T cell exclusion and infiltrating macrophages. Associations of immune-poor CIN GEAs with MYC activity and CCNE1 amplification may enable new studies to determine precise mechanisms of immune evasion, ultimately inspiring new therapeutic modalities.

Meta-analysis of preoperative high-sensitivity cardiac troponin measurement in non-cardiac surgical patients at risk of cardiovascular complications.

BACKGROUND: Patients undergoing major non-cardiac surgery are at risk of cardiovascular complications. Raised levels of high-sensitivity troponin are frequently detected before operation among these patients. However, the prognostic value of high-sensitivity troponin in predicting postoperative outcomes remains unclear. METHODS: A systematic search of PubMed, Embase and Science Citation Index Expanded was undertaken for observational studies published before March 2018 that reported associations between raised preoperative levels of high-sensitivity troponin and postoperative major adverse cardiac events and/or mortality after non-cardiac surgery. Meta-analyses were performed, where possible, using random-effects models. RESULTS: Seven cohort studies with a total of 4836 patients were included. A raised preoperative high-sensitivity troponin level was associated with a higher risk of short-term major adverse cardiac events (risk ratio (RR) 2·92, 95 per cent c.i. 1·96 to 4·37; I2  = 82·6 per cent), short-term mortality (RR 5·39, 3·21 to 9·06; I2  = 0 per cent) and long-term mortality (RR 2·90, 1·83 to 4·59, I2  = 74·2 per cent). The addition of preoperative high-sensitivity troponin measurement provided improvements in cardiovascular risk discrimination (increase in C-index ranged from 0·058 to 0·109) and classification (quantified by continuous net reclassification improvement) compared with Lee's Revised Cardiac Risk Index alone. There was substantial heterogeneity and inadequate risk stratification analysis in the included studies. CONCLUSION: Raised preoperative levels of high-sensitivity troponin appear to represent a risk for postoperative major adverse cardiac events and mortality. Further study is required before high-sensitivity troponin can be used to predict risk stratification in routine clinical practice.

ANTECEDENTES: Los pacientes a los que se realiza una cirugía mayor no cardíaca tienen riesgo de presentar complicaciones cardiovasculares. En estos pacientes se observan con frecuencia niveles preoperatorios elevados de troponina de alta sensibilidad (high-sensitivity troponin, hs-cTn). Sin embargo, el valor pronóstico de la hs-cTn para predecir los resultados postoperatorios no está bien definido. MÉTODOS: Se realizó una búsqueda sistemática en las bases de datos PubMed, EMBASE y Science Citation Index Expanded de estudios observacionales publicados antes de marzo de 2018 que analizasen la posible relación de los niveles elevados preoperatorios de hs-cTn y los efectos adversos graves de tipo cardíaco (major adverse cardiac events, MACE) postoperatorios y/o la mortalidad después de la cirugía no cardíaca. Se realizó el metaanálisis utilizando modelos de efectos aleatorios siempre que fuera posible. RESULTADOS: Se incluyeron siete estudios de cohortes con un total de 4.836 pacientes. La elevación preoperatoria de hs-cTn se asoció con un mayor riesgo de MACE a corto plazo (tasa de riesgo, risk ratio, RR 2,92, i.c. del 95% 1,96-4,37, I2 = 82,6%) y con la mortalidad a corto plazo (RR 5,39, i.c. del 95 % 3,21-9,06, I2 = 0%) y a largo plazo (RR 2,90, i.c. del 95% 1,83-4,59, I2 = 74,2%). Añadir la medición preoperatoria de hs-cTn mejoró la capacidad discriminativa para el riesgo cardiovascular (aumento de 5,8% a 10,9% en el índice C) y también la clasificación de los pacientes (cuantificada mediante el índice de reclasificación neta continua) en comparación con el uso de solo el índice de riesgo cardíaco revisado de Lee. En los estudios incluidos, hubo gran heterogeneidad y análisis inadecuado de la estratificación del riesgo. CONCLUSIÓN: Los niveles preoperatorios elevados de troponina de alta sensibilidad parecen ser un marcador de riesgo de efectos adversos graves de tipo cardíaco en el postoperatorio y de mortalidad. Se requieren más estudios antes de utilizar la troponina de alta sensibilidad para la estratificación del riesgo en la práctica clínica rutinaria.

Effect and possible mechanisms of dioscin on ameliorating metabolic glycolipid metabolic disorder in type-2-diabetes.

BACKGROUND: Our previous study revealed that microRNA-125a-5p plays a crucial role in regulating hepatic glycolipid metabolism by targeting STAT3 in type 2 diabetes mellitus (T2DM). Dioscin, a major active ingredient in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in T2DM has not been reported. PURPOSE: The aim of this study was to investigate the effect of dioscin on T2DM and elucidate its potential mechanism. METHODS: The effect of dioscin on glycolipid metabolic disorder in insulin-induced HepG2 cells, palmitic acid-induced AML12 cells, high-fat diet- and streptozotocin- induced T2DM rats, and spontaneous T2DM KK-Ay mice were evaluated. Then, the possible mechanisms of dioscin were comprehensively evaluated. RESULTS: Dioscin markedly alleviated the dysregulation of glycolipid metabolism in T2DM by reducing hyperglycemia and hyperlipidemia, improving insulin resistance, increasing hepatic glycogen content, and attenuating lipid accumulation. When the mechanism was investigated, dioscin was found to markedly elevate miR-125a-5p level and decrease STAT3 expression. Consequently, dioscin increased phosphorylation levels of STAT3, PI3K, AKT, GSK-3ß, and FoxO1 and decreased gene levels of PEPCK, G6Pase, SREBP-1c, FAS, ACC, and SCD1, leading to an increase in glycogen synthesis and a decrease in gluconeogenesis and lipogenesis. The effects of dioscin on regulating miR-125a-5p/STAT3 pathway were verified by miR-125a-5p overexpression and STAT3 overexpression. CONCLUSIONS: Dioscin showed potent anti-T2DM activity by improving the inhibitory effect of miR-125a-5p on STAT3 signaling to alleviate glycolipid metabolic disorder of T2DM.

[The roles of TSP-1 and its receptor CD47 in pathogenesis of paraquat-induced pulmonary fibrosis in rats].

Objective: To establish a rat model of paraquat (PQ) -induced pulmonary fibrosis and observe the changes in thrombospondin-1 (TSP-1) and its receptor CD47 in lung tissue, and to investigate their roles in the pathogenesis of PQ-induced pulmonary fibrosis. Methods: Fifty-four clean adult male Sprague-Dawley rats were randomly divided into normal control group (n=6) and 2 h, 12 h, 1 d, 3 d, 7 d, and 14 d PQ poisoning groups (n=8 per group). A rat model of PQ poisoning was established by a single gavage of 20 wt.% PQ solution (50 mg/kg). Flow cytometry was used to determine the concentration of reactive oxygen species (ROS) in blood and lung tissue. Enzyme-linked immunosorbent assay was used to determine the concentrations of hydroxyl radicals, malondialdehyde, and hydroxyproline in lung tissue. HE staining and Masson staining were used to observe the pathological damage of lung tissue after PQ poisoning. The expression of TSP-1 and CD47 in lung tissue was measured by Immunohistochemistry. Results: Compared with the normal control group, the 2 h to 7 d PQ poisoning groups showed significant increases in ROS fluorescence intensity in red blood cells and lung tissues and the concentrations of malondialdehyde and hydroxyl radicals in lung tissue (P<0.05) , and the 14 d PQ poisoning group had a significant increase in the concentration of hydroxyproline in lung tissue (P<0.05). HE staining showed that the 2 h to 7 d PQ poisoning groups had significantly higher semiquantitative pathological scores of pulmonary alveolitis than the normal control group (P<0.05). The Masson staining showed that the 7 d and 14 d PQ poisoning groups had significantly higher semiquantitative pathological scores of pulmonary fibrosis than the normal control group (P<0.05). Compared with the normal control group, all PQ poisoning groups (except the 12 h group) had significantly increased expression of TSP-1 in lung tissue (P<0.05) , and all PQ poisoning groups (except the 1 d group) had significantly increased expression of CD47 in lung tissue (P<0.05). Within 2 h after PQ poisoning, the expression of TSP-1 and CD47 was positively correlated with the concentrations of ROS, hydroxyl radicals, and malondialdehyde and the degree of pulmonary alveolitis (P<0.01) ; at 1 d after PQ poisoning, the expression of TSP-1 and CD47 was positively correlated with the concentration of hydroxyproline in lung tissue (P<0.01) . Conclusion: The expression of TSP-1 and CD47 is closely related to oxidative stress and subsequent pulmonary fibrosis, and they may be involved in the development and progression of pulmonary alveolitis and subsequent pulmonary fibrosis in rats with PQ poisoning.

Critical scaling of icosahedral medium-range order in CuZr metallic glass-forming liquids.

The temperature evolution of icosahedral medium-range order formed by interpenetrating icosahedra in CuZr metallic glassforming liquids was investigated via molecular dynamics simulations. Scaling analysis based on percolation theory was employed, and it is found that the size distribution of clusters formed by the central atoms of icosahedra at various temperatures follows a very good scaling law with the cluster number density scaled by S-τ and the cluster size S scaled by |1 - Tc/T|-1/σ, respectively. Here Tc is scaling crossover-temperature. τ and σ are scaling exponents. The critical scaling behaviour suggests that there would be a structural phase transition manifested by percolation of locally favoured structures underlying the glass transition, if the liquid could be cooled slowly enough but without crystallization intervening. Furthermore, it is revealed that when icosahedral short-range order (ISRO) extends to medium-range length scale by connection, the atomic configurations of ISROs will be optimized from distorted ones towards more regular ones gradually, which significantly lowers the energies of ISROs and introduces geometric frustration simultaneously. Both factors make key impacts on the drastic dynamic slow-down of supercooled liquids. Our findings provide direct structure-property relationship for understanding the nature of glass transition.

[The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China].

OBJECTIVE: To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations. METHODS: In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015. RESULTS: As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study. CONCLUSIONS: INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

Chronic blockade of class I PI3-kinase attenuates Ang II-induced cardiac hypertrophy and autophagic alteration.

OBJECTIVE: Chronic Ang II stimulation is linked to cardiac remodeling characterized by fibrosis and cardiac hypertrophy. However, the underlying cellular mechanisms involved are not yet fully known. Here, we studied the molecular mechanisms underlying the chronic effect of Ang II on cardiac hypertrophy, fibrosis, and autophagy. MATERIALS AND METHODS: The role of class I PI3-kinase in these actions of Ang II was studied using lentiviral vector-mediated expression of a dominant negative form of PI3-kinase subunit p85α (Lv-DNp85) in the heart. Ang II was infused subcutaneously for 4 weeks on rats using osmotic pumps. Cardiac hypertrophy, fibrosis, reactive oxygen species (ROS), and autophagy were examined in four groups of rats (Ang II+Lv-DNp85, Ang II+Lv-GFP, Saline+Lv-DNp85, Saline+Lv-GFP). RESULTS: Chronic infusion of Ang II induced severe cardiac hypertrophy and perivascular fibrosis in the heart. These effects were associated with a significant reduction in LC3 II and elevation in ROS levels, suggesting marked impairment of cardiac autophagy and increased generation of ROS. Cardiac transduction of Lv-DNp85 significantly attenuated Ang II-induced impairment of autophagy and elevation of ROS, as well as Ang II-induced cardiac hypertrophy and perivascular fibrosis. To study the cellular mechanisms underlying those actions of Ang II, phosphorylated Akt and mTOR were measured in hearts from these rats. Ang II increased phosphorylation of Akt and mTOR; and cardiac transduction of Lv-DNp85 significantly abolished Ang II-induced phosphorylation of Akt and mTOR, a signaling pathway inhibiting autophagy. CONCLUSIONS: These results demonstrate that class I PI3-kinase, via activation of the Akt-mTOR pathway, is involved in Ang II-induced impairment of autophagy, elevation of ROS, cardiac hypertrophy, and fibrosis, suggesting a novel target for cardiac protection.

Hidden topological order and its correlation with glass-forming ability in metallic glasses.

Unlike the well-defined long-range periodic order that characterizes crystals, so far the inherent atomic packing mode in glassy solids remains mysterious. Based on molecular dynamics simulations, here we find medium-range atomic packing orders in metallic glasses, which are hidden in the diffraction data in terms of structure factors or pair correlation functions. The analysis of the hidden orders in various metallic glasses indicates that the glassy and crystalline solids share a nontrivial structural homology in short-to-medium range, and the hidden orders are formulated by inheriting partial crystalline orders during glass formation. As the number of chemical components increases, more hidden orders are often developed in a metallic glass and entangled topologically. We use this phenomenon to explain the geometric frustration in glass formation and the glass-forming ability of metallic alloys.

Effect analysis of early bedside hemo-filtration in treatment of severe pneumonia with acute renal failure of children.

OBJECTIVE: To investigate the best opportunity for bedside continuous blood purification (CBP) to treat severe pneumonia with acute renal failure (ARF) of children and look for the sensitive marker to evaluate the clinical effects and prognosis. PATIENTS AND METHODS: 54 children patients that were diagnosed as severe pneumonia with ARF by Pediatric Intensive Care Unit (PICU) were enrolled in our study as experimental group. In the meanwhile, 46 children patients that were diagnosed as severe pneumonia with ARF by PICU were enrolled as a normal control group. Patients in the experimental group started CBP treatment within 24 h after onset while patients in the control group started CBP treatment 24h after onset. The differences of clinical effects between two groups were compared for statistical significance. RESULTS: The survival rates of the observation group in day 7, day 28 and 6 months were significantly higher than those in the control group. After treatment for 7 days, IL-6 and TNF-α, YKL-40 and Annexin A1 levels of the experimental group were significantly lower than those of the control group. 7-day infection-related organ failure score (SOFA) of the experimental group was significantly lower than that of the control group. CONCLUSIONS: CBP therapy for treating severe pneumonia with acute renal failure of children within 24 hours could significantly improve the survival rate and reduce the inflammatory reactions.

Safety culture in a pharmacy setting using a pharmacy survey on patient safety culture: a cross-sectional study in China.

OBJECTIVE: To explore the attitudes and perceptions of patient safety culture for pharmacy workers in China by using a Pharmacy Survey on Patient Safety Culture (PSOPSC), and to assess the psychometric properties of the translated Chinese language version of the PSOPSC. DESIGN: Cross-sectional study. PARTICIPANTS: Data were obtained from 20 hospital pharmacies in the southwest part of China. METHODS: We performed χ(2) test to explore the differences on pharmacy staff in different hospital and qualification levels and countries towards patient safety culture. We also computed descriptive statistics, internal consistency coefficients and intersubscale correlation analysis, and then conducted an exploratory factor analysis. A test-retest was performed to assess reproducibility of the items. RESULTS: A total of 630 questionnaires were distributed of which 527 were responded to validly (response rate 84%). The positive response rate for each item ranged from 37% to 90%. The positive response rate on three dimensions ('Teamwork', 'Staff Training and Skills' and 'Staffing, Work Pressure and Pace') was higher than that of Agency for Healthcare Research and Quality (AHRQ) data (p<0.05). There was a statistical difference in the perception of patient safety culture at different hospital and qualification levels. The internal consistency of the total survey was comparatively satisfied (Cronbach's α=0.89). CONCLUSIONS: The results demonstrated that among the pharmacy staffs surveyed in China, there was a positive attitude towards patient safety culture in their organisations. Identifying perspectives of patient safety culture from pharmacists in different hospital and qualification levels are important, since this can help support decisions about action to improve safety culture in pharmacy settings. The Chinese translation of the PSOPSC questionnaire (V.2012) applied in our study is acceptable.

Role of 15-F2t-isoprostane in intestinal injury induced by intestinal ischemia/reperfusion in rats.

15-F2t-isoprostane is not only a specific marker of lipid peroxidation but also demonstrated to have potent bioactivities and can exert deleterious effects via activating thromboxane A2 receptor (TxA2r). We already demonstrated that lipid peroxidation represents a mechanism of intestinal ischemia/reperfusion (I/R) injury. But no studies have focused on 15-F2t-isoprostane production and its biological actions on postischemic intestine during intestinal I/R. This study was carried to investigate whether the mechanism of endogenous 15-F2t-isoprostane action is involved in the pathogenesis of intestinal I/R and administration of synthetic 15-F2t-isoprostane could exacerbate intestinal insult after intestinal I/R in vivo and in vitro. In comparison with that of the sham control, we reported that endogenous 15-F2t-isoprostane was liberated following intestinal I/R injury in rats, and using the TxA2r antagonist SQ29548 resulted in significant intestinal protection, evidenced by reduced lipid peroxidation, inflammation, and alleviated intestinal mucosal microvascular vasoconstriction. Further research found that in vivo administration of synthetic 15-F2t-isoprostane exacerbated intestinal I/R injury by disturbing microvascular perfusion and accumulating anaerobic metabolism. Meanwhile, 15-F2t-isoprostane did not change Hypoxia/Reoxygenation-induced IEC-6 cell viability but aggravated HUVECs cell death in vitro. Collectively, our results showed that locally produced 15-F2t-isoprostane was in proportion to the severity of oxidative stress-induced intestinal injury and its detrimental effects can be attenuated through TxA2r inactivation. Exogenous 15-F2t-isoprostane exacerbated intestinal I/R injury, which may be contributable to its biological actions on endothelium, rather than intestinal epithelium.

Dexmedetomidine reduces intestinal and hepatic injury after hepatectomy with inflow occlusion under general anaesthesia: a randomized controlled trial.

BACKGROUND: We compared intestinal, hepatic, and other organ function after hepatic portal occlusion with or without dexmedetomidine administration under general anaesthesia. METHODS: In this prospective, randomized double-blind investigation, 44 patients undergoing elective hepatectomy with inflow occlusion were randomized into a dexmedetomidine group or a control group. The dexmedetomidine group received an initial dexmedetomidine loading dose of 1 µg kg(-1) over 10 min followed by a maintenance dose of 0.3 µg kg(-1) h(-1). In the control group, 0.9% sodium chloride was administered. The primary outcome was serum diamine oxidase (DAO) activity reflecting intestinal injury. The secondary outcomes included variables reflecting intestinal, hepatic, kidney, and cardiopulmonary function, and biomarkers of oxidative stress and systemic inflammatory response. RESULTS: DAO activity was lower in the dexmedetomidine group than in the control group at 6 and 24 h after liver reperfusion [9.77 (1.07) vs14.29 (1.43) units ml(-1), P=0.021; 9.67 (0.98) vs 13.97 (1.31) units ml(-1), P=0.017]. d-lactate acid levels were lower during 1-72 h after liver reperfusion compared with the control group (all P<0.05). Also, the intestinal injury severity grade was decreased by dexmedetomidine (P=0.038). The biomarkers reflecting liver injury increased over time, but were lower in the dexmedetomidine group (all P<0.05), while the variables reflecting cardiopulmonary and renal function showed no differences between the groups (all P>0.05). CONCLUSIONS: Dexmedetomidine administered perioperatively attenuates intestinal and hepatic injury in patients undergoing elective liver resection with inflow occlusion without any potential risk. CLINICAL TRIAL REGISTRATION: ChiCTR-TRC-11001530, September 2011.

Comparison of extracts from cooked and raw lentil in antagonizing angiotensin II-induced hypertension and cardiac hypertrophy.

AIM: The objective of this study is to examine effects of extracts from cooked lentils on angiotensin II (Ang II)-induced hypertension, cardiac hypertrophy and fibrosis in normotensive rats. MATERIALS AND METHODS: Animals were divided into four groups (n=5 each group): control group, Ang II group, Ang II plus cooked lentil extract (Ang II+CLE) group, and Ang II plus raw lentil extract (Ang II+RLE) group. The telemetry blood pressure transducers were implanted into all rats. A telemetry BP probe was positioned intra-abdominally and secured to the ventral abdominal muscle with the catheter inserted into the lower abdominal aorta. Heart wall thickness, cross-sectional area of cardiomyocytes, diameter of the arterial cross-sections, and perivascular fibrosis in heart and kidney were measured. The surface area of positive-staining cardiomyocytes was analyzed using image analysis software. Reactive oxygen species (ROS) generation was determined using an oxidant-sensitive fluorogenic probe. RESULTS: Rats that received cooked or raw lentil extracts (oral administration, 8 weeks) show significantly attenuated Ang II-induced elevation in blood pressure, cardiac hypertrophy, perivascular fibrosis. Results demonstrated that pretreatment of cardiomyocytes with cooked or raw lentil extract significantly attenuated the Ang II-induced increase in the size of cells (16.0±1.7% and 21.2±2.9%, respectively, n=5, p < 0.05), and cooked or raw lentil extracts also attenuated the Ang II-induced increase in the reactive oxygen species levels in cardiomyocytes (19.8±2.2% & 26.6±3.1%, respectively, n=5, p < 0.05). CONCLUSIONS: This study showed that extracts from cooked lentils could prevent Ang II-induced elevation in blood pressure, cardiac hypertrophy, small arterial remodeling and perivascular fibrosis, and heating process does not have any significant affect on these protective effects.

Effect of local structures on structural evolution during crystallization in undercooled metallic glass-forming liquids.

The effect of local structures on structural evolution during the crystallization of undercooled ZrCu metallic glass-forming liquid was studied via molecular dynamics simulations. It is found that body-centered-cubic (bcc)-like clusters play a key role in structural evolution during crystallization. In contrast to previous speculations, the number of bcc-like crystal nuclei does not change much before the onset of crystallization. Instead, the development of a bcc-like critical nucleus during annealing leads to a strong spatial correlation with other nuclei in its surroundings, forming a crystalline structure template. It is also found that the size distribution of bcc-like nuclei follows a power-law form with an exponential cutoff in the early stage of annealing, but changes to a pure power-law behavior just before the onset of crystallization. This implies that the crystalline structure template has fractal feature and the undercooled liquids evolve to a self-organized critical state before the onset of crystallization, which might trigger the subsequent rapid crystallization. According to the graph theory analysis, it is also found that the observed large scatter of the onset time of crystallization in different liquid samples results from the connectivity of the bcc-like clusters.

Isolation and identification of metabolites of osthole in rats.

Osthole (Ost), one of the major components of Cnidium monnieri (L.) Cusson, is had the structure of an isopentenoxy-coumarin with a range of pharmacological activities. In the present study, the metabolism of Ost in male Sprague-Dawley rats was investigated by identifying Ost metabolites excreted in rat urine. Following an oral dose of 40 mg/kg Ost, 10 phase I and 3 phase II metabolites were isolated from the urine of rats, and their structures identified on the basis of a range of spectroscopic data, including 2D-NMR techniques. These metabolites were fully characterized as 5'-hydroxyl-osthole (M-1), osthenol (M-2), 4'-hydroxyl-osthole (M-3), 3, 5'-dihydroxyl-osthole (M-4), 5'-hydroxyl-osthenol (M-5), 4'-hydroxyl-2', 3'-dihydro-osthenol (M-6), 4'-hydroxyl-osthenol (M-7), 3, 4'-dihydroxyl-osthole (M-8), 2', 3'-dihydroxyl-osthole (M-9), 5'-hydroxyl-2', 3'-dihydroosthole (M-10), osthenol-7-O-ß-D-glucuronide (M-11), osthole-4'-O-ß-D-glucuronide (M-12) and osthole-5'-O-ß-D-glycuronate (M-13). This is the first identification of M-1, M-3 to M-13 in vivo. On the basis of the metabolites profile, a possible metabolic pathway for Ost metabolism in rats has been proposed. This is the first systematic study on the phases I and II metabolites of 8-isopentenoxy-coumarin derivative.