Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.

INTRODUCTION: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses. RESULTS: A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, P = 3.68×10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10-7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD-associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. HIGHLIGHTS: Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies. The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa. Single variant meta-analysis identified a novel genome-wide significant AD-risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome-wide significance at P < 9×10-7. Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus. These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry-informed genetic screening tools and therapeutic interventions.

Somatosensory game intervention experience among prefrail older adults in the community: A qualitative study.

BACKGROUND: Somatosensory game interventions have been used to rehabilitate hospitalized older adults. However, their application in prefrail older adults in the community is poorly understood, hindering the development of effective intervention strategies and exercise diversification. OBJECTIVES: This study aimed to explore the experiences of prefrail Chinese older adults engaging in somatosensory gaming interventions and thus develop tailored intervention frameworks and support strategies. METHODS: We conducted semistructured interviews with 12 prefrail older adults who participated in a 12-week sensory game intervention study from August to September 2022. The interviews were analyzed using Nvivo 11.0 software following Colaizzi's seven-step analysis method. RESULTS: Somatosensory game intervention experiences were classified into four main themes and 11 subthemes: health intervention effects (enhanced limb muscle strength, improved reaction capacity, alleviated negative emotions), positive experiences (enhanced self-achievement, increased exercise motivation, elevated social engagement), negative experiences (frustration from unmet score expectations, initial discomfort), and intervention requirements (sustained interventions, technical support, personalized content). CONCLUSION: The findings have implications for somatosensory game interventions targeting prefrail older adults in the community.

STAG2 mutations regulate 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme.

Inactivating mutations of genes encoding the cohesin complex are common in a wide range of human cancers. STAG2 is the most commonly mutated subunit. Here we report the impact of stable correction of endogenous, naturally occurring STAG2 mutations on gene expression, 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme (GBM). In two GBM cell lines, correction of their STAG2 mutations significantly altered the expression of ∼10% of all expressed genes. Virtually all the most highly regulated genes were negatively regulated by STAG2 (i.e., expressed higher in STAG2-mutant cells), and one of them-HEPH-was regulated by STAG2 in uncultured GBM tumors as well. While STAG2 correction had little effect on large-scale features of 3D genome organization (A/B compartments, TADs), STAG2 correction did alter thousands of individual chromatin loops, some of which controlled the expression of adjacent genes. Loops specific to STAG2-mutant cells, which were regulated by STAG1-containing cohesin complexes, were very large, supporting prior findings that STAG1-containing cohesin complexes have greater loop extrusion processivity than STAG2-containing cohesin complexes and suggesting that long loops may be a general feature of STAG2-mutant cancers. Finally, STAG2 mutation activated Polycomb activity leading to increased H3K27me3 marks, identifying Polycomb signaling as a potential target for therapeutic intervention in STAG2-mutant GBM tumors. Together, these findings illuminate the landscape of STAG2-regulated genes, A/B compartments, chromatin loops, and pathways in GBM, providing important clues into the largely still unknown mechanism of STAG2 tumor suppression.

Integrative approach for predicting drug-target interactions via matrix factorization and broad learning systems.

In the drug discovery process, time and costs are the most typical problems resulting from the experimental screening of drug-target interactions (DTIs). To address these limitations, many computational methods have been developed to achieve more accurate predictions. However, identifying DTIs mostly rely on separate learning tasks with drug and target features that neglect interaction representation between drugs and target. In addition, the lack of these relationships may lead to a greatly impaired performance on the prediction of DTIs. Aiming at capturing comprehensive drug-target representations and simplifying the network structure, we propose an integrative approach with a convolution broad learning system for the DTI prediction (ConvBLS-DTI) to reduce the impact of the data sparsity and incompleteness. First, given the lack of known interactions for the drug and target, the weighted K-nearest known neighbors (WKNKN) method was used as a preprocessing strategy for unknown drug-target pairs. Second, a neighborhood regularized logistic matrix factorization (NRLMF) was applied to extract features of updated drug-target interaction information, which focused more on the known interaction pair parties. Then, a broad learning network incorporating a convolutional neural network was established to predict DTIs, which can make classification more effective using a different perspective. Finally, based on the four benchmark datasets in three scenarios, the ConvBLS-DTI's overall performance out-performed some mainstream methods. The test results demonstrate that our model achieves improved prediction effect on the area under the receiver operating characteristic curve and the precision-recall curve.

Elucidating carbon conversion and bacterial succession by amending Fenon-like systems during co-composting of pig manure and branch.

The essential point of current study was to investigate the effect of a Fenton-like system established by oxalic acid and Fe(II) on gas emission, organic matter decomposition and humification during composting. Branches were pretreated with Fenton reagents (0.02 M FeCl2·4H2O + 1.5 M H2O2) and then adding 10 % oxalic acid (OA). The treatments were marked as B1 (control), B2 (Fenton reagent), B3 (10% OA) and B4 (Fenton-like reagent). The results collected from 80 d of composting showed that adding Fenton-like reagent benefited the degradation of organic substances, as reflected by the total organic carbon and dissolved organic carbon, and the maximum decomposition rate was observed in B4. In addition, the Fenton-like reagent could improve the synthesis of humus characterized by complex and stable compounds, which was consistent with the spectral parameters (SUVA254, SUVA280, E253/E203 and Fourier transform-infrared indicators) of DOC. Furthermore, the functional microbial succession performance and linear discriminant effect size analyses provided microbial evidence of humification improvement. Notably, compared with the control, the minimum value of CH4 cumulation was reported in B4, which decreased by 30.44 %. Concluded together, the addition of a Fenton-like reagent composed by OA and Fe(II) is a practical way to improve the humification. Furthermore, the mechanisms related to the promotion of humification should be investigated from free radicals, functional genes, and metabolic pathways.

Higher High-Mobility Group Box-1 Levels are Associated with White Matter Lesions in Ischemic Stroke Patients.

Background and Purpose: High-mobility group box-1 (HMGB1) is a useful biomarker for disease severity stratification and prognosis prediction. We aim to explore whether the circulating HMGB1 concentrations are associated with the white matter lesions (WMLs) burden in stroke patients. Methods: Between 2022 June and December 2022, patients with acute ischemic stroke were prospectively enrolled. HMGB1 levels were measured by an enzyme-linked immunosorbent assay after admission for all patients. The WMLs severity was assessed by the Fazekas scale. We dichotomized patients into those with moderate-severe WMLs (Fazekas score 3-6) versus those with none-mild WMLs (Fazekas score 0-2). Furthermore, based on the severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs), patients were categorized as none-mild (Fazekas score 0-1) or moderate-severe (Fazekas score 2-3). Results: A total of 287 participants (mean age: 64.9 years; 157 male) were analyzed. The median serum HMGB1 levels were 7.3 ng/mL (interquartile, 4.3 ng/mL-12.3 ng/mL). After adjustment for potential confounders, elevated HMGB1 levels were associated with the presence of moderate-severe WMLs (first quartile vs fourth quartile, odds ratio [OR], 4.101; 95% confidence interval [CI], 1.948-8.633; P = 0.001) and moderate-severe PWMLs (first quartile vs fourth quartile, OR, 9.181; 95% CI, 4.078-20.671; P = 0.001). Similar results were found when the HMGB1 levels were analyzed as a continuous variable. Conclusion: This study demonstrated that increased HMGB1 levels were associated with the severity of WMLs, mainly in the periventricular region.

Exploring carbon conversion and balance with magnetite-amended during pig manure composting.

This study was designed to explore the magnetite in maturation and humification during pig manure (PM) and wolfberry branch fillings (BF) composting. Different proportions of magnetite (T1, 0%; T2, 2.5%; T3, 5%; T4, 7.5%;) were blended with PM for 50 days of composting. The findings indicated magnetite amendment has no influence on the maturity, and the 5% ratio significantly promoted humic acid (HA) formation and fulvic acid (FA) decomposition compared to other treatments. Compared to T1, magnetite addition significantly increased CO2 and CH4 emissions by 106.39%-191.69% and 6.88-13.72 times. The further analysis suggested that magnetite improved Ruminofilibacter activity were significantly positively associated with HA, and C emissions. The further PICRUSt 2 analysis showed membrane transport may enhance environmental information processing by magnetite. Overall, these results demonstrated higher organic matter (OM) degradation and HA formation with an additional increase in microbial activity highlighted advantages of using magnetite during PM composting.

Association of age and night flight duration with sleep disorders among Chinese airline pilots.

Objective: Night flights might aggravate sleep disorders among aging airline pilots, posing a threat to flight safety. In this study, we assess the prevalence of sleep disorders as well as the combined effects of night flight duration and aging on sleep disorders. Method: A cross-sectional study was conducted between July and December, 2021. Participants were recruited from a commercial airline. Sleep disorders were evaluated using the Pittsburgh Sleep Quality Index (PSQI). The interaction effect of night flight duration and age on sleep disorders and their correlates were examined using logistic regression models. Results: In total, 1,208 male airline pilots were included in the study, with a median age of 34 (interquartile range [IQR]: 29-39) years. The overall prevalence of sleep disorders was 42.6%. The multivariate logistic regression identified an interaction between night flight duration and age on sleep disorders (adjusted odds ratio [aOR] of the interaction term was 5.85 95% CI: 2.23-15.34 for age ≥ 45 years; 1.96 95% CI:1.01-3.81 for the age group 30-44 years). Longer night flight duration (aOR: 4.55; 95%CI: 1.82-11.38) and body mass index (BMI) ≥28.0 kg/m2 (aOR: 0.16; 95% CI: 0.03-0.91) were significantly associated with sleep disorders in participants aged ≥45 years. Hyperuricemia (aOR: 1.54; 95% CI: 1.09-2.16) and regular exercise (aOR: 0.23; 95% CI: 0.08-0.70) were significantly associated with sleep disorders in the 30-44 years age group. Conclusion: The mean monthly night flight duration and aging had a synergistic effect on airline pilots' sleep disorders, implying an aging and work-related mechanistic pathogenesis of sleep disorders in airline pilots that requires additional exploration and intervention.

A novel composting system for mitigating ammonia emissions and producing nitrogen-rich organic fertilizer.

Ammonia emissions not only lead to environmental pollution but also reduce the quality of compost products. Here, a novel composting system (condensation return composting system, CRCS) was designed for mitigating ammonia emissions. The results showed that the CRCS reduced ammonia emissions by 59.3% and increased the total nitrogen content by 19.4% compared with the control. By integrating the results of nitrogen fraction conversion, ammonia-assimilating enzyme activity, and structural equation modeling, it was found that the CRCS facilitated the conversion of ammonia to organic nitrogen by stimulating ammonia-assimilating enzyme activity and ultimately retained nitrogen in the compost product. Moreover, the pot experiment confirmed that nitrogen-rich organic fertilizer produced by the CRCS significantly increased the fresh weight (45.0%), root length (49.2%), and chlorophyll content (11.7%) of pakchoi. This study provides a promising strategy for mitigating ammonia emissions and producing nitrogen-rich organic fertilizer with high agronomic value.

Timing of Fungal Insecticide Application to Avoid Solar Ultraviolet Irradiation Enhances Field Control of Rice Planthoppers.

Thechemical control of rice planthoppers (RPH)is prohibited in annual rice-shrimp rotation paddy fields. Here, the fungal insecticides Beauveria bassiana ZJU435 and Metarizhium anisoplae CQ421 were tested for control of RPH populations dominated by Nilaparvata lugens in three field trials. During four-week field trials initiated from the harsh weather of high temperatures and strong sunlight, the rice crop at the stages from tillering to flowering was effectively protected by fungal sprays applied at 14-day intervals. The sprays of either fungal insecticide after 5:00 p.m. (solar UV avoidance) suppressed the RPH population better than those before 10 a.m. The ZJU435 and CQ421 sprays for UV avoidance versus UV exposure resulted in mean control efficacies of 60% and 56% versus 41% and 45% on day 7, 77% and 78% versus 63% and 67% on day 14, 84% and 82% versus 80% and 79% on day 21, and 84% and 81% versus 79% and 75 on day 28, respectively. These results indicate that fungal insecticides can control RPH in the rice-shrimp rotation fields and offer a novel insight into the significance of solar-UV-avoiding fungal application for improved pest control during sunny summers.

Improvement of Arsenic Tolerance and Removal Ability of Multi-stress-tolerant Pichia kudriavzevii A16 by Salt Preincubation.

Arsenic (As) exists widely in the environment and its strong toxicity endangers human health, causing widespread concern. Microbial adsorption technology plays an important role in As removal due to its advantages of high safety, low pollution, and low cost. The removal of As by active microorganisms requires not only good accumulation characteristics but also high As tolerance. The effect of salt preincubation on arsenate [As(V)] tolerance and bioaccumulation of Pichia kudriavzevii A16 and the possible mechanisms were studied. Salt preincubation improved the As(V) tolerance and bioaccumulation ability of the yeast. After Na5P3O10 preincubation, the proportion of dead cells and cells with high reactive oxygen species (ROS) accumulation decreased from 50.88% and 16.54% to 14.60% and 5.24%, respectively. In addition, the As removal rate significantly increased from 26.20% to 57.98%. The preincubated cells showed stronger As(V) tolerance and removal ability. The potential of use in complex environment to remove As(V) as well as the mechanisms involved in As(V) tolerance by yeast will be discussed.

In Vivo Assessment of the Effects of Mono-Carrier Encapsulated Fucoxanthin Nanoparticles on Type 2 Diabetic C57 Mice and Their Oxidative Stress.

Fucoxanthin (FX) is a carotenoid from a marine origin that has an important role in our health, especially in the regulation and alleviation of type 2 diabetes. Its specific molecular structure makes it very unstable, which greatly affects its delivery in the body. In this study, FX was encapsulated in a mono-carrier using a hydrolyzed zein to form a nanocomplex with a stable structure and chemical properties (FZNP). Its stability was demonstrated by characterization and the efficacy of FX before and after encapsulation in alleviating diabetes in mice, which was evaluated by in vivo experiments. FZNP reduced the level of fasting blood glucose and restored it to normal levels in T2DM mice, which was not caused by a decrease in food intake, and effectively reduced oxidative stress in the organism. Both FX and FZNP repaired the hepatocyte and pancreatic ß-cell damage, increased serum SOD and reduced INS values significantly, upregulated PI3K-AKT genes as well as CaMK and GNAs expression in the pancreas. FZNP increased ADPN and GSH-PX values more significantly and it decreased serum HOMA-IR and MDA values, upregulated GLUT2 expression, promoted glucose transport in pancreatic and hepatocytes, regulated glucose metabolism and glycogen synthesis with much superior effects than FX.

DeepLoop robustly maps chromatin interactions from sparse allele-resolved or single-cell Hi-C data at kilobase resolution.

Mapping chromatin loops from noisy Hi-C heatmaps remains a major challenge. Here we present DeepLoop, which performs rigorous bias correction followed by deep-learning-based signal enhancement for robust chromatin interaction mapping from low-depth Hi-C data. DeepLoop enables loop-resolution, single-cell Hi-C analysis. It also achieves a cross-platform convergence between different Hi-C protocols and micrococcal nuclease (micro-C). DeepLoop allowed us to map the genetic and epigenetic determinants of allele-specific chromatin interactions in the human genome. We nominate new loci with allele-specific interactions governed by imprinting or allelic DNA methylation. We also discovered that, in the inactivated X chromosome (Xi), local loops at the DXZ4 'megadomain' boundary escape X-inactivation but the FIRRE 'superloop' locus does not. Importantly, DeepLoop can pinpoint heterozygous single-nucleotide polymorphisms and large structure variants that cause allelic chromatin loops, many of which rewire enhancers with transcription consequences. Taken together, DeepLoop expands the use of Hi-C to provide loop-resolution insights into the genetics of the three-dimensional genome.

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes.

Tea polysaccharide (TPS) is a bioactive compound that has attracted increasing attention for its health effect on regulating the metabolism of glucose and lipid. Moreover, due to their good biocompatibility and biodegradability, TPS-based nanoparticles have emerged as effective nanocarriers for the delivery of bioactive molecules. In this study, we developed a TPS-based biocarrier system for the orally targeted administration of Mn(II) ions and investigated their antidiabetic effects in C57BL/6 mice with HFD/streptozotocin (STZ)-induced T2DM. Mn(II)-loaded TPS-based nanoparticles (MTNPs) were synthesized, in which negatively charged functional groups in protein and uronic acid in TPS conjugates would act as binding sites for Mn(II) ions, which is responsible for the cross-linking reaction of MTNP. The resulting MTNP had a spherical shape and a mean particle size of around 30 nm with a Mn(II) ion content of 2.24 ± 0.13 mg/g. In T2DM mice, we discovered that MTNP treatment significantly lowered blood glucose levels and improved glucose intolerance. Furthermore, the impact of MTNP on the recovery of FINS, the homeostatic index of insulin resistance (HOMA-IR), and the homeostatic index of ß-cell (HOMA ß-cell) levels was significantly larger (p < 0.05) than TPS alone, demonstrating that Mn(II) ions can enhance TPS's ability to repair HFD/STZ-induced ß-cell damage. Mn(II) ions in MTNP not only acted as cofactors to increase the exocytosis of insulin secretory cells by upregulating the expression of Ca(II)/calmodulin-dependent protein kinase II (CaMK II) but also promoted TPS's lipid-lowering effect in T2DM mice by inhibiting glucogenesis and regulating the lipid metabolism. Our findings suggest that Mn(II) ions can be used not only as cross-linkers in the formation of nanoparticulated TPS but also as cofactors in improving the functional role of TPS in regulating the glucose and lipid metabolism, which will provide insights into the development of TPS-based drug delivery systems for the prevention of type 2 diabetes.

Circulating microbial content in myeloid malignancy patients is associated with disease subtypes and patient outcomes.

Although recent work has described the microbiome in solid tumors, microbial content in hematological malignancies is not well-characterized. Here we analyze existing deep DNA sequence data from the blood and bone marrow of 1870 patients with myeloid malignancies, along with healthy controls, for bacterial, fungal, and viral content. After strict quality filtering, we find evidence for dysbiosis in disease cases, and distinct microbial signatures among disease subtypes. We also find that microbial content is associated with host gene mutations and with myeloblast cell percentages. In patients with low-risk myelodysplastic syndrome, we provide evidence that Epstein-Barr virus status refines risk stratification into more precise categories than the current standard. Motivated by these observations, we construct machine-learning classifiers that can discriminate among disease subtypes based solely on bacterial content. Our study highlights the association between the circulating microbiome and patient outcome, and its relationship with disease subtype.

[VOCs Emission Inventory and Uncertainty Analysis of Industry in Qingdao Based on Latin Hypercube Sampling and Monte Carlo Method].

In recent years, fine particulate matter(PM2.5) and ozone(O3) have become the main air pollutants in cities in China. Volatile organic compounds(VOCs) are one of the important precursors of PM2.5, O3, and secondary organic aerosols. The establishment of VOCs emission inventory is therefore of great significance for controlling the amount of PM2.5 and O3. To date, the coefficient method has been used, which has error transmission of activity level, parameter and model, leading to the uncertainty of emission inventory. Multivariate uncertainty quantitative analysis of VOCs emission inventory provides an accurate alternative which has not been reported in China. The bottom-up method is adopted to collect the activity level of each enterprise. The variables of pollution control measures are obtained from surveys conducted with enterprises. The VOCs emission inventory of Qingdao from industrial source is established using an optimized coefficient method. The uncertainty of the VOCs inventory on the impact of univariate and multivariate variables is simulated by combining the Monte Carlo method(MC) with Latin hypercube sampling method(LHS). The results show that the total VOCs emissions were 44700 tons from industrial sources in 2019(unoptimized coefficient method:31100 tons).The rubber and plastic industries, metal products, and oil/coal/other fuel processing contributed more VOCs, which accounted for 40.26% of the total emissions. The uncertainty of multivariate simulation is higher than that of single variable. The uncertainty from process(-9.72%-230.51%) and solvent using source(-14.14%-122.77%) is significantly higher than uncertainty from combustion source(-15.62%-36.41%). The main sectors affecting the uncertainty of the VOCs inventory include:the chemical, papermaking, and textile industries(emission factors); metal, automobile manufacturing, and chemical industries(removal rate, facility operating rate); industries of petroleum processing and ferrous metal smelting(too few samples). VOCs emissions are mainly distributed in the east of the West Coast New district, north of Dazhu Mountain, south of Jimo district, north of Chengyang district, northeast of Jiaozhou district, built-up area of Pingdu district, and southeast of Laixi district.

Experimental data on the adsorption of water by branches and leaves as affected by different the morphological characteristics of plants.

We determined 116 globally important woody tree species, classified them based on the differences between plant life-forms, leaf textures and trichomes on leaves and measured the indices of some plant morphological traits in the Guizhou karstic regions of China. The water adsorbed on the upper surfaces of branches and leaves and the water adsorbed on the upper and lower surfaces of branches and leaves (WWu and WWul) of these species was measured. The ratios of the weight of adsorbed water on the upper surfaces of branches and leaves to the weight of branches and leaves (RWWu) and the ratios of the weight of adsorbed water on the upper and lower surfaces of branches and leaves to the weight of branches and leaves (RWWul) were calculated. The adsorption of water and morphological trait indices follow the approximately normal distributions. The weight of branches and leaves (weight), total leaf area (TLA) and mean leaf area (MLA) significantly impacted the adsorption of water by branches and leaves. The different rates of the adsorption of water for 116 tree species can explain the interspecific variation in rainfall interception. Interpretation of these data is provided in Effects of the morphological characteristics of plants on rainfall interception and kinetic energy[J]. Journal of Hydrology, 2020: 125807. https://doi.org/10.1016/j.jhydrol.2020.125807.

The effect of physician educational intervention on venous thromboembolism pharmacological prophylaxis in medical inpatients from the respiratory department: a retrospective cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a serious health problem for which pharmacological prophylaxis has been proven to be effective. However, there are significant gaps between the guidelines and clinical practice. This study is to evaluate the effect of physician educational intervention (PEI) on VTE pharmacological prophylaxis in medical inpatients from the respiratory department. METHODS: Medical inpatients from the respiratory department between February 2014 and December 2016 were recruited in this retrospective cohort study. They were assigned to the PEI group or the control group according to whether their physicians undertook a quality improvement (QI) project carried out in hospital to raise physician awareness of pharmacological thromboprophylaxis by educational intervention. Any and appropriate pharmacological VTE prophylaxis rates, the use of appropriate anticoagulants, and the occurrence of VTE events in the two groups were calculated and compared using a chi-square test and continuity correction. Poisson regression analysis was used to evaluate the relative risk (RR) of PEI on the occurrence of VTE events. RESULTS: The any pharmacological VTE prophylaxis rate (11.3% vs. 5.9%, P=0.048) and appropriate pharmacological VTE prophylaxis rate (9.3% vs. 5.5%, P=0.036) in high-risk patients without high major bleeding risk were both significantly higher than the control group. Compared with the control group, appropriate anticoagulants in the PEI group took up a larger proportion of all used anticoagulants (90.3% vs. 78.7%, P=0.007). In anticoagulants used for high-risk patients without high major bleeding, appropriate anticoagulants show no statistical difference between the two groups (93.8% vs. 77.8%, P=0.153). There was no difference in the occurrence of VTE events between the two study groups in overall patients (0.5% vs. 0.6%, P=0.913), and among those with high VTE risk (1.7% vs. 1.0%, P=0.554). PEI had no association with the probability of VTE event occurrence (RR, 1.246; 95% CI, 0.478-2.188, P=0.954). CONCLUSIONS: Educational intervention effectively increased physician awareness of VTE prophylaxis in the respiratory department. Further interventions are still necessary since the guidelines were implemented to a relatively low degree.

Hydrocortisone decreases lethality and inflammatory cytokine and nitric oxide production in rats challenged with B. anthracis cell wall peptidoglycan.

BACKGROUND: Lethal B. anthracis infection produces high proinflammatory peptidoglycan (PGN) burdens in hosts. We investigated whether the lethality and inflammation anthrax PGN can produce are related. METHODS: At 6 h before and the start of 24 h anthrax PGN infusions, rats (n = 198) were treated with diluent (controls) or one of three IV-doses of either hydrocortisone (125, 12.5 or 1.25 mg/kg) or TNF-soluble receptor (TNFsr; 2000, 1000 or 333 µg/kg), non-selective and selective anti-inflammatory agents, respectively. RESULTS: Compared to controls, hydrocortisone 125 and 12.5 mg/kg each decreased 7-day lethality (p ≤ 0.004). Hydrocortisone 125 mg/kg decreased IL-1ß, IL-6, TNFα, MCP, MIP-1α, MIP-2, RANTES and nitric oxide (NO) blood levels at 4 and 24 h after starting PGN (except MCP at 24 h). Each decrease was significant at 4 h (except MIP-1α that was significant at 24 h) (p ≤ 0.05). Similarly, hydrocortisone 12.5 mg/kg decreased each measure at 4, 24 and 48 h (except TNFα at 24 h and MIP-1α at 24 and 48 h and NO at 48 h). Decreases were significant for IL-6 and NO at 4 h and RANTES at 48 h (p ≤ 0.05). Hydrocortisone 1.25 mg/kg had non-significant effects. Each TNFsr dose decreased lethality but non-significantly. However, when doses were analyzed together, TNFsr decreased lethality in a potential trend (p = 0.16) and IL-6 and NO significantly at 4 h (p = 0.05). CONCLUSIONS: Peptidoglycan-stimulated host inflammation may contribute to B. anthracis lethality.

Tanshinone IIA exerts therapeutic effects by acting on endogenous stem cells in rats with liver cirrhosis.

BACKGROUND AND OBJECTIVE: Liver cirrhosis (LC), the major pathway for the progression and development of chronic liver disease, is an advanced stage of liver disease. It is the third most common chronic noncommunicable disease after cardiovascular diseases and malignant tumors. Tanshinone IIA (Tan), an extract of Salvia miltiorrhiza (S. miltiorrhiza), has been proven to promote the proliferation and differentiation of stem cells. Moreover, its protective effect in liver injury has received widespread attention. The present study investigated whether Tan plays a therapeutic role in LC by promoting endogenous stem cell proliferation and differentiation. MATERIALS AND METHODS: LC models were established by intraperitoneal injection of an olive oil solution containing 50 % carbon tetrachloride (CCL4) combined with 10 % alcohol in the drinking water. After successful model establishment, the animals were randomly divided into four groups and injected with physiological saline or low-, medium-, or high-dose (10, 20, or 40 mg/kg) Tan for seven consecutive days. The protective effect of Tan on LC was observed by western blotting, serological examination and histopathological staining. Furthermore, immunofluorescence double-labeling of 5-bromo-2-deoxyuridine (BrdU) and the liver cell markers albumin and CK-18 or the liver stem cell markers EPCAM and OV-6 was used to evaluate the proliferation and differentiation of endogenous liver stem cells. RESULTS: We confirmed successful establishment of the LC model by observing transaminase levels and hematoxylin-eosin (HE) and Masson staining of liver sections in CCL4-treated and healthy rats. After Tan treatment, HE and Masson staining of paraffin sections of liver tissue showed that Tan treatment significantly improved histological injury to the liver. Serological tests showed that albumin-bilirubin (ALBI) scores and models for end-stage liver disease (MELD) were lower. Immunofluorescence and immunohistochemical staining showed that the newly proliferated cells were colocalized with ALB, OV-6, EPCAM, and CK-18, indicating that new expression of these markers occurred after Tan injection. All results were most significant in the medium-dose treatment group. CONCLUSION: Tan can alleviate liver injury induced by CCL4 combined with alcohol in rats and plays a therapeutic role in LC by promoting the proliferation and differentiation of endogenous liver stem cells.