Trace elements apportionment in forage, soil, and livestock in rangeland ecosystems along climatic gradients.

BACKGROUND: Alpine meadows, typical steppes, and deserts are among the globally important rangeland types that are generally distributed along temperature and precipitation gradients. Mineral losses caused by grazing are one of the key factors that can lead to instability or even degradation of these rangeland ecosystems. METHODS: We examined the concentrations of Cu, Fe, Mn, and Zn in soil, forage, and livestock dungs from diverse rangeland types in northwest China, to determine the relationships between these trace elements (TEs) concentrations and climatic factors (i.e., temperature, precipitation, and humidity), and to evaluate the potential risks of TEs deficiencies or excesses in these rangeland ecosystems. RESULTS: Forage Zn concentrations in forage of all three types of rangeland, and Cu concentrations in forage of the alpine meadow did not meet the growth requirements of grazing livestock. Concentrations of Cu, Fe, and Mn in forage and Fe, Mn, and Zn in livestock dungs had quadratic parabola relationships with temperature, precipitation, and humidity, but the relationships between climate factors and Cu, Fe, and Mn concentrations in soil were not significant. In addition, the abilities of the plant to absorb Cu, Fe, and Zn from soil were stronger in the typical steppe than that in the alpine meadows and desert. Also, the abilities of livestock to return TEs to soil were stronger in the alpine meadow than that in the typical steppe and desert. CONCLUSION: We derived a conceptual mode that the ratio of TE concentrations of the plant to soil and of livestock dung to forage represents the abilities of plants to absorb TEs from the soil matrix and livestock to return TEs to soil or to absorb TEs from forage, respectively. Results indicate potentially more serious risks of TEs deficiencies, especially that of Zn than previously considered in typical steppes and desert rangelands.

Learning to predict in-hospital mortality risk in the intensive care unit with attention-based temporal convolution network.

BACKGROUND: Dynamic prediction of patient mortality risk in the ICU with time series data is limited due to high dimensionality, uncertainty in sampling intervals, and other issues. A new deep learning method, temporal convolution network (TCN), makes it possible to deal with complex clinical time series data in ICU. We aimed to develop and validate it to predict mortality risk using time series data from MIMIC III dataset. METHODS: A total of 21,139 records of ICU stays were analysed and 17 physiological variables from the MIMIC III dataset were used to predict mortality risk. Then we compared the model performance of the attention-based TCN with that of traditional artificial intelligence (AI) methods. RESULTS: The area under receiver operating characteristic (AUCROC) and area under precision-recall curve (AUC-PR) of attention-based TCN for predicting the mortality risk 48 h after ICU admission were 0.837 (0.824 -0.850) and 0.454, respectively. The sensitivity and specificity of attention-based TCN were 67.1% and 82.6%, respectively, compared to the traditional AI method, which had a low sensitivity (< 50%). CONCLUSIONS: The attention-based TCN model achieved better performance in the prediction of mortality risk with time series data than traditional AI methods and conventional score-based models. The attention-based TCN mortality risk model has the potential for helping decision-making for critical patients. TRIAL REGISTRATION: Data used for the prediction of mortality risk were extracted from the freely accessible MIMIC III dataset. The project was approved by the Institutional Review Boards of Beth Israel Deaconess Medical Center (Boston, MA) and the Massachusetts Institute of Technology (Cambridge, MA). Requirement for individual patient consent was waived because the project did not impact clinical care and all protected health information was deidentified. The data were accessed via a data use agreement between PhysioNet, a National Institutes of Health-supported data repository (https://www.physionet.org/), and one of us (Yu-wen Chen, Certification Number: 28341490). All methods were carried out in accordance with the institutional guidelines and regulations.

Effects of circadian rhythm on Narcotrend index and target-controlled infusion concentration of propofol anesthesia.

BACKGROUND: The effects of circadian rhythms on drug metabolism and efficacy are being increasingly recognized. However, the extent to which they affect general anesthesia remains unclear. This study aims to investigate the effects of circadian rhythms on anesthetic depth and the concentrations of propofol target-controlled infusion (TCI). METHODS: Sixty patients undergoing laparoscopic surgeries were sequentially assigned to four groups. Group ND (n = 15): Propofol TCI with Narcotrend monitor during the day (8:00-18:00), Group NN (n = 15): Propofol TCI with Narcotrend monitor during the night (22:00-5:00), Group CLTD (n = 15): Propofol closed-loop TCI guided by bispectral index (BIS) during the day (8:00-18:00), Group CLTN (n = 15): Propofol closed-loop TCI guided by BIS during the night (22:00-5:00). The Narcotrend index, mean arterial pressure (MAP) and heart rate (HR) were compared between group ND and NN at 7 time points, from 5 min before induction to the end of operation. The propofol TCI concentrations, MAP and HR were compared between group CLTD and CLTN at 7 time points, from 5 min after induction to the end of operation. RESULTS: The Narcotrend index, MAP, and HR in group NN were lower than those in group ND from the beginning of mechanical ventilation to the end of operation (p < 0.05). The propofol TCI concentrations in group CLTN were lower than those in group CLTD from the beginning of operation to the end of operation (p < 0.05). CONCLUSION: Circadian rhythms have a significant effect on the depth of anesthesia and drug infusion concentrations during propofol TCI. When using general anesthesia during night surgery, the propofol infusion concentration should be appropriately reduced compared to surgery during the day. TRIAL REGISTRATION: The present study was registered on the ClinicalTrials.gov website ( NCT02440269 ) and approved by the Medical Ethics Committee of Southwest Hospital of Third Military Medical University (ethics lot number: 2016 Research No. 93). All patients provided informed written consent to participate in the study.

AMD3100 treatment attenuates pulmonary angiogenesis by reducing the c-kit (+) cells and its pro-angiogenic activity in CBDL rat lungs.

Recent studies have shown that pulmonary angiogenesis is an important pathological process in the development of hepatopulmonary syndrome (HPS), and growing evidence has indicated that Stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis is involved in pulmonary vascular disease by mediating the accumulation of c-kit+ cells. This study aimed to test the effect of AMD3100, an antagonist of CXCR4, in HPS pulmonary angiogenesis. Common bile duct ligation (CBDL) rats were used as experimental HPS model and were treated with AMD3100 (1.25mg/kg/day, i.p.) or 0.9% saline for 3weeks. The sham rats underwent common bile duct exposure without ligation. The c-kit+ cells accounts and its angiogenic-related functions, prosurvival signals, pulmonary angiogenesis and arterial oxygenation were analysed in these groups. Our results showed that pulmonary SDF-1/CXCR4, Akt, Erk and VEGF/VEGFR2 were significantly activated in CBDL rats, and the numbers of circulating and pulmonary c-kit+ cells were increased in CBDL rats compared with control rats. Additionally, the angiogenic-related functions of c-kit+ cells and pulmonary microvessel counts were also elevated in CBDL rats. CXCR4 inhibition reduced pulmonary c-kit+ cells and microvessel counts and improved arterial oxygenation within 3weeks in CBDL rats. The pulmonary prosurvival signals and pro-angiogenic activity of c-kit+ cells were also down-regulated in AMD3100-treated rats. In conclusion, AMD3100 treatment attenuated pulmonary angiogenesis in CBDL rats and prevented the development of HPS via reductions in pulmonary c-kit+ cells and inhibition of the prosurvival signals. Our study provides new insights in HPS treatment.

Dynamin-related protein 1-mediated mitochondrial fission contributes to post-traumatic cardiac dysfunction in rats and the protective effect of melatonin.

Mechanical trauma (MT) causes myocardial injury and cardiac dysfunction. However, the underlying mechanism remains largely unclear. This study investigated the role of mitochondrial dynamics in post-traumatic cardiac dysfunction and the protective effects of melatonin. Adult male Sprague Dawley rats were subjected to 5-minute rotations (200 revolutions at a rate of 40 rpm) to induce MT model. Melatonin was administrated intraperitoneally 5 minute after MT. Mitochondrial morphology, myocardial injury, and cardiac function were determined in vivo. There was smaller size of mitochondria and increased number of mitochondria per µm2 in the hearts after MT when the secondary myocardial injury was induced. Melatonin treatment at the dose of 30 mg/kg reduced serine 616 phosphorylation of Drp1 and inhibited mitochondrial Drp1 translocation and mitochondrial fission in the hearts of rats subjected to MT, which contributed to the reduction of myocardial injury and the improvement of cardiac function. In vitro, H9c2 cells cultured in 20% traumatic plasma (TP) for 12 hour showed enhanced mitochondrial fission, mitochondrial membrane potential (∆Ψm) loss, mitochondrial cytochrome c release, and decreased mitochondrial complex I-IV activities. Pretreatment with melatonin (100 µmol/L) efficiently inhibited TP-induced mitochondrial fission, ∆Ψm loss, cytochrome c release, and improved mitochondrial function. Melatonin's protective effects were attributed to its role in suppressing plasma TNF-α overproduction, which was responsible for Drp1-mediated mitochondrial fission. Taken together, our results demonstrate for the first time that abnormal mitochondrial dynamics is involved in post-traumatic cardiac dysfunction. Melatonin has significant pharmacological potential in protecting against MT-induced cardiac dysfunction by preventing excessive mitochondrial fission.

The angiogenic related functions of bone marrow mesenchymal stem cells are promoted by CBDL rat serum via the Akt/Nrf2 pathway.

Hepatopulmonary syndrome (HPS) is a complication of severe liver disease. It is characterized by an arterial oxygenation defect. Recent studies have demonstrated that pulmonary angiogenesis contributes to the abnormal gas exchange found in HPS. Additionally, mesenchymal stem cells (MSCs) are considered the stable source of VEGF-producing cells and have the potential to differentiate into multiple cell types. However, it has not been determined whether bone marrow mesenchymal stem cells (BM-MSCs) are mobilized and involved in the pulmonary angiogenesis in HPS. In this study, a CFU-F assay showed that the number of peripheral blood MSCs was increased in common bile duct ligation (CBDL) rats; however, there was no significant difference found in the number of BM-MSCs. In vitro, CBDL rat serum induced the overexpression of CXCR4 and PCNA in BM-MSCs. Consistently, the directional migration as well as the proliferation ability of BM-MSCs were enhanced by CBDL rat serum, as determined by a transwell migration and MTT assays. Moreover, the secretion of VEGF by BM-MSCs increased after treatment with CBDL rat serum. We also found that the expression of phospho-Akt, phospho-ERK, and Nrf2 in BM-MSCs was significantly up-regulated by CBDL rat serum in a time dependent manner, and the blockage of the Akt/Nrf2 signalling pathway with an Akt Inhibitor or Nrf2 siRNA, instead of an ERK inhibitor, attenuated the migration, proliferation and paracrine capacity of BM-MSCs. In conclusion, these findings indicated that the number of MSCs increased in the peripheral blood of CBDL rats, and the Akt/Nrf2 pathway plays a vital role in promoting the angiogenic related functions of BM-MSCs, which could be a potent contributor to pulmonary angiogenesis in HPS.

Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated the role of deferoxamine (DFO), a clinically used iron chelator, in a mouse model of surgery-induced cognitive dysfunction and assessed its neuroprotective effects on neuroinflammation, oxidative stress, and memory function. METHODS: A model of laparotomy under general anesthesia and analgesia was used to study POCD. Twelve to 14 months C57BL/6J male mice were treated with DFO, and changes in iron signaling, microglia activity, oxidative stress, inflammatory cytokines, and neurotrophic factors were assessed in the hippocampus on postoperative days 3, 7, and 14. Memory function was evaluated using fear conditioning and Morris water maze tests. BV2 microglia cells were used to test the anti-inflammatory and neuroprotective effects of DFO. RESULTS: Peripheral surgical trauma triggered changes in hippocampal iron homeostasis including ferric iron deposition, increase in hepcidin and divalent metal transporter-1, reduction in ferroportin and ferritin, and oxidative stress. Microglia activation, inflammatory cytokines, brain-derived neurotropic factor impairments, and cognitive dysfunction were found up to day 14 after surgery. Treatment with DFO significantly reduced neuroinflammation and improved cognitive decline by modulating p38 MAPK signaling, reactive oxygen species, and pro-inflammatory cytokines release. CONCLUSIONS: Iron imbalance represents a novel mechanism underlying surgery-induced neuroinflammation and cognitive decline. DFO treatment regulates neuroinflammation and microglia activity after surgery.

Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling.

Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling.

Caspase-3 inhibition prevents the development of hepatopulmonary syndrome in common bile duct ligation rats by alleviating pulmonary injury.

BACKGROUND & AIMS: Common bile duct ligation (CBDL) rats is an accepted experimental model of hepatopulmonary syndrome (HPS), defined as liver disease and intrapulmonary vascular dilatation and hypoxaemia. Pulmonary Akt and ERK activation followed by angiogenesis in the later stages of CBDL, contribute to the pathogenesis of HPS. However, the mechanisms behind Akt and ERK activation remain undefined. Pulmonary injury induced by increased bilirubin, endotoxin and inflammatory mediators occurs in the early stages of CBDL. We assessed the effects of relieving pulmonary injury on Akt and ERK activation and on the development of HPS following CBDL. METHODS: Pulmonary injury, angiogenesis, arterial oxygenation, cell proliferation and, phospho-Akt and ERK1 were evaluated in CBDL animals with or without caspase-3 inhibition (Z-DEVD-FMK). Pulmonary injury was assessed by histology and quantifying apoptosis and aquaporin-1 (AQP1) levels. Lung angiogenesis was assessed by quantifying AQP1 level, vWF-positive cells and microvessel count. RESULTS: Pulmonary apoptosis and caspase-3 activation were markedly increased in the early stages of CBDL. Caspase-3 inhibition alleviated apoptosis, the reduction in AQP1, phospho-Akt and ERK1 levels and pulmonary injury 1 week after CBDL. Caspase-3 inhibition also reduced AQP1, phospho-Akt and ERK1 levels, vWF-positive cells, cell proliferation, microvessel count, and microvascular dilatation and improved arterial oxygenation 3 weeks following CBDL. CONCLUSIONS: Caspase-3 inhibition alleviates pulmonary injury, thereby preventing angiogenesis as well as the development of HPS in CBDL rats. These effects are related to the regulation of the Akt and ERK1 pathways.

MiR-206 controls the phenotypic modulation of pulmonary arterial smooth muscle cells induced by serum from rats with hepatopulmonary syndrome by regulating the target gene, annexin A2.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver disease that is characterised by intrapulmonary vascular dilatation (IPVD) and arterial hypoxemia. Pulmonary vascular remodelling (PVR) is an important pathological feature of HPS, but the potential mechanisms underlying PVR remain undefined. Recent findings have established the essential role of changes in Annexin A2 (ANXA2) in controlling the phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs) in PVR associated with HPS. However, the mechanism by which upstream signalling regulates ANXA2 is unclear. METHODS: In the present study, computational analysis was used to predict which miRNA might target the 3´-untranslated region (3´-UTR) of the ANXA2 mRNA. Real-time PCR and western blotting were performed to study the level of correlation between ANXA2 and the differentiation marker with the predicted miRNAs in PASMCs stimulated with serum from normal rats or those with HPS. Functional analysis of the miRNA and a luciferase reporter assay were performed to demonstrate that the predicted miRNA suppressed ANXA2 expression by directly targeting the predicted 3´-UTR site of the ANXA2 mRNA. RESULTS: Computational analysis predicted that miR-206 would target the 3´-UTR of ANXA2 mRNA. In HPS rat serum-stimulated PASMCs, the expression of miR-206 displayed an inverse correlation with ANXA2, while a positive correlation was observed with the phenotypic marker smooth muscle α-actin (SM α-actin). The miRNA functional analysis and luciferase reporter assay demonstrated that miR-206 effectively downregulated the expression of ANXA2 by binding to the 3´-UTR of the ANXA2 mRNA. Consistently, miR-206 effectively inhibited the HPS rat serum-induced phenotypic modulation and proliferation, while these effects were reversed in ANXA2-overexpressing PASMCs. CONCLUSION: This study demonstrates that miR-206 inhibits the HPS rat serum-induced phenotypic modulation and proliferation in PASMCs by down-regulating ANXA2 gene expression.

Dietary supplementation of Allium mongolicum modulates rumen-hindgut microbial community structure in Simmental calves.

Compared to traditional herbage, functional native herbage is playing more important role in ruminant agriculture through improving digestion, metabolism and health of livestock; however, their effects on rumen microbial communities and hindgut fermentation are still not well understood. The objective of present study was to evaluate the effects of dietary addition of Allium mongolicum on bacterial communities in rumen and feces of claves. Sixteen 7-month-old male calves were randomly divided into four groups (n = 4). All calves were fed a basal ration containing roughage (alfalfa and oats) and mixed concentrate in a ratio of 60:40 on dry matter basis. In each group, the basal ration was supplemented with Allium mongolicum 0 (SL0), 200 (SL200), 400 (SL400), and 800 (SL800) mg/kg BW. The experiment lasted for 58 days. Rumen fluid and feces in rectum were collected, Rumen fluid and hindgut fecal were collected for analyzing bacterial community. In the rumen, Compared with SL0, there was a greater relative abundance of phylum Proteobacteria (p < 0.05) and genera Rikenellaceae_RC9_gut_group (p < 0.01) in SL800 treatment. In hindgut, compared with SL0, supplementation of A. mongolicum (SL200, SL400, or SL800) decreased in the relative abundances of Ruminococcaceae_UCG-014 (p < 0.01), Ruminiclostridium_5 (p < 0.01), Eubacterium_coprostanoligenes_group (p < 0.05), and Alistipes (p < 0.05) in feces; Whereas, the relative abundances of Christensenellaceae_R-7_group (p < 0.05), and Prevotella_1 (p < 0.01) in SL800 were higher in feces, to maintain hindgut stability. This study provided evidence that A. mongolicum affects the gastrointestinal of calves, by influencing microbiota in their rumen and feces.

Appropriate N fertilizer addition mitigates N2O emissions from forage crop fields.

Forage crops are widely cultivated as livestock feed to relieve grazing pressure in agro-pastoral regions with arid climates. However, gaseous losses of soil nitrogen (N) following N fertilizer application have been considerable in response to the pursuit of increased crop yield. A two-year experiment was carried out in a typical saline field under a temperate continental arid climate to investigate the effect of N application rate on N2O emissions from barley (Hordeum vulgare L.), corngrass (Zea mays × Zea Mexicana), rye (Secale cereale L.), and sorghum-sudangrass hybrid (Sorghum bicolor × Sorghum sudanense). The dynamics of N2O emissions, hay yield, and crude protein (CP) yield were measured under four N application rates (0, 150, 200, and 250 kg ha-1) in 2016 and 2017. An N2O emission peak was observed for all crop species five days after each N application. Cumulative N2O fluxes in the growing season ranged from 0.66 to 2.40 kg ha-1 and responded exponentially to N application rate. Emission factors of N2O showed a linear increase with N application rate for all crop species, but the linear slopes significantly differed between barley or rye and corngrass and sorghum-sudangrass hybrid. The hay and CP yields of all forage grasses significantly increased with the increase of N application rate from 0 to 200 kg ha-1. Barley and rye with lower hay and CP yields showed higher N2O emission intensities. The increased level of N2O emission intensity was higher from 200 to 250 kg ha-1 than from 150 to 200 kg ha-1. At N application rates of 200 and 250 kg ha-1, CP yield had a significantly negative correlation with cumulative N2O emission and explained 50.5% and 62.9% of the variation, respectively. In conclusion, ~200 kg ha-1 is the optimal N rate for forage crops to minimize N2O emission while maintaining yield in continental arid regions.

Aitongxiao improves pain symptoms of rats with cancer pain by reducing IL-1, TNF-α, and PGE2.

OBJECTIVE: To explore the mechanism of Aitongxiao in improving pain symptoms of rats with cancer pain. METHODS: Walker 256 breast cancer cells were injected into the right tibial bone marrow cavity of normal female rats to establish a rat model of tibial cancer pain. The rats with successful model replication were randomly divided into normal group (NG), Hank solution group (HSG), cancer pain model group (CPMG), and Aitongxiao+cancer pain model group (ATX+CPMG). The pain response score, mechanical pain hindpaw withdrawal threshold, and latent heat pain of rats were evaluated, and the changes of serum IL-1ß, TNF-α, PGE2 and blood cell counts of rats were detected. RESULTS: Compared with the NG, the pain response score was increased, the mechanical pain hindpaw withdrawal threshold and latent heat pain were decreased, and IL-1ß, TNF-α, and PGE2 were increased in CPMG. Compared with the CPMG, the pain response score was decreased, the mechanical pain hindpaw withdrawal threshold and latent heat pain were increased, and IL-1ß, TNF-α, and PGE2 were decreased in ATX+CPMG. There was no significant change in blood cell count in each group. CONCLUSION: Aitongxiao can improve the pain symptoms of rats with tibial cancer pain. Its mechanism may be related to the reduction of IL-1ß, TNF-α, and PGE2 levels.

A Simple and Quick Screening Method for Intrapulmonary Vascular Dilation in Cirrhotic Patients Based on Machine Learning.

BACKGROUND AND AIMS: Screening for hepatopulmonary syndrome in cirrhotic patients is limited due to the need to perform contrast enhanced echocardiography (CEE) and arterial blood gas (ABG) analysis. We aimed to develop a simple and quick method to screen for the presence of intrapulmonary vascular dilation (IPVD) using noninvasive and easily available variables with machine learning (ML) algorithms. METHODS: Cirrhotic patients were enrolled from our hospital. All eligible patients underwent CEE, ABG analysis and physical examination. We developed a two-step model based on three ML algorithms, namely, adaptive boosting (termed AdaBoost), gradient boosting decision tree (termed GBDT) and eXtreme gradient boosting (termed Xgboost). Noninvasive variables were input in the first step (the NI model), and for the second step (the NIBG model), a combination of noninvasive variables and ABG results were used. Model performance was determined by the area under the curve of receiver operating characteristics (AUCROCs), precision, recall, F1-score and accuracy. RESULTS: A total of 193 cirrhotic patients were ultimately analyzed. The AUCROCs of the NI and NIBG models were 0.850 (0.738-0.962) and 0.867 (0.760-0.973), respectively, and both had an accuracy of 87.2%. For both negative and positive cases, the recall values of the NI and NIBG models were both 0.867 (0.760-0.973) and 0.875 (0.771-0.979), respectively, and the precisions were 0.813 (0.690-0.935) and 0.913 (0.825-1.000), respectively. CONCLUSIONS: We developed a two-step model based on ML using noninvasive variables and ABG results to screen for the presence of IPVD in cirrhotic patients. This model may partly solve the problem of limited access to CEE and ABG by a large numbers of cirrhotic patients.

Herbicide applications increase greenhouse gas emissions of alfalfa pasture in the inland arid region of northwest China.

Herbicides are used to control weeds in agricultural crops such as alfalfa (Medicago sativa L.), which is a forage crop. It is unclear what, if any, effect herbicides have on greenhouse gas (GHG) emissions when used on alfalfa. Our study was conducted in 2017 and 2018 to investigate the effects of two herbicides (Quizalofop-p-ethyl, QE and Bentazone, BT) on methane (CH4), carbon dioxide (CO2) and nitrous oxide (N2O) emissions from soil planted with alfalfa. QE is used to control grasses and BT is used for broadleaf weed control. Soil CO2 emissions and soil uptake of CH4 increased significantly in both years following the QE and BT treatments, although CO2 emissions differed significantly between the trial years. N2O emissions decreased relative to the control and showed no significant differences between the trial years. The application of QE and BT on alfalfa resulted in a significant increase in CO2 emissions which contributed to a significant increase in GHG emissions. The application of QE influenced GHG emissions more than BT. We demonstrated the potential effect that herbicide applications have on GHG fluxes, which are important when considering the effect of agricultural practices on GHG emissions and the potential for global warming over the next 100 years.

Optimizing alfalfa productivity and persistence versus greenhouse gases fluxes in a continental arid region.

Alfalfa in China is mostly planted in the semi-arid or arid Northwest inland regions due to its ability to take up water from deep in the soil and to fix atmospheric N2 which reduces N fertilizer application. However, perennial alfalfa may deplete soil water due to uptake and thus aggravate soil desiccation. The objectives of this study were (1) to determine the alfalfa forage yield, soil property (soil temperature (ST), soil water content (SWC), soil organic carbon (SOC) and soil total nitrogen (STN)) and greenhouse gas (GHG: methane (CH4), nitrous oxide (N2O), and carbon dioxide (CO2)) emissions affected by alfalfa stand age and growing season, (2) to investigate the effects of soil property on GHG emissions, and (3) to optimize the alfalfa stand age by integrating the two standard criteria, the forage yield and water use efficiency, and the total GHG efflux (CO2-eq). This study was performed in alfalfa fields of different ages (2, 3, 5 and 7 year old) during the growing season (from April to October) in a typical salinized meadow with temperate continental arid climate in the Northwest inland regions, China. Despite its higher total GHG efflux (CO2-eq), the greater forage yield and water use efficiency with lower GEIhay and high CH4 uptake in the 5-year alfalfa stand suggested an optimal alfalfa stand age of 5 years. Results show that ST, SOC and RBM alone had positive effects (except RBM had no significant effect on CH4 effluxes), but SWC and STN alone had negative effects on GHG fluxes. Furthermore, results demonstrate that in arid regions SWC superseded ST, SOC, STN and RBM as a key factor regulating GHG fluxes, and soil water stress may have led to a net uptake of CH4 by soils and a reduction of N2O and CO2 effluxes from alfalfa fields. Our study has provided insights into the determination of alfalfa stand age and the understanding of mechanisms regulating GHG fluxes in alfalfa fields in the continental arid regions. This knowledge is essential to decide the alfalfa retention time by considering the hay yield, water use efficiency as well as GHG emission.

A better method for the dynamic, precise estimating of blood/haemoglobin loss based on deep learning of artificial intelligence.

BACKGROUND: Dynamic and precise estimation of blood loss (EBL) is quite important for perioperative management. To date, the Triton System, based on feature extraction technology (FET), has been applied to estimate intra-operative haemoglobin (Hb) loss but is unable to directly assess the amount of blood loss. We aimed to develop a method for the dynamic and precise EBL and estimate Hb loss (EHL) based on artificial intelligence (AI). METHODS: We collected surgical patients' non-recycled blood to generate blood-soaked sponges at a set gradient of volume. After image acquisition and preprocessing, FET and densely connected convolutional networks (DenseNet) were applied for EBL and EHL. The accuracy was evaluated using R2, the mean absolute error (MAE), the mean square error (MSE), and the Bland-Altman analysis. RESULTS: For EBL, the R2, MAE and MSE for the method based on DenseNet were 0.966 (95% CI: 0.962-0.971), 0.186 (95% CI: 0.167-0.207) and 0.096 (95% CI: 0.084-0.109), respectively. For EHL, the R2, MAE and MSE for the method based on DenseNet were 0.941 (95% CI: 0.934-0.948), 0.325 (95% CI: 0.293-0.355) and 0.284 (95% CI: 0.251-0.317), respectively. The accuracies of EBL and EHL based on DenseNet were more satisfactory than that of FET. Bland-Altman analysis revealed a bias of 0.02 ml with narrow limits of agreement (LOA) (-0.47 to 0.52 mL) and of 0.05 g with narrow LOA (-0.87 to 0.97 g) between the methods based on DenseNet and actual blood loss and Hb loss. CONCLUSIONS: We developed a simpler and more accurate AI-based method for EBL and EHL, which may be more fit for surgeries primarily using sponges and with a small to medium amount of blood loss.

Efficacy observation on prevention of chemotherapy-related anemia by combined therapy of traditional Chinese medicine in malignant tumors / 肿瘤研究与临床

Objective:To explore the effect of combined therapy of traditional Chinese medicine on prevention of chemotherapy-related anemia in malignant tumors.Methods:Seventy-nine patients with malignant tumors diagnosed in Zibo Hospital of Traditional Chinese Medicine from January 2019 to January 2021 were selected, and the patients were divided into experimental group (40 cases) and control group (39 cases) according to the random number table method. The control group received chemotherapy and the experimental group received chemotherapy and combined therapy of traditional Chinese medicine (Wuhong Tang combined with moxibustion). The hemoglobin (Hb) level, Karnofsky score and adverse effects were recorded before and on days 7, 14 and 21 after chemotherapy in the two groups.Results:The Hb level in the experimental group was higher than that in the control group [(117±28) g/L vs. (100±31) g/L] on day 21 after chemotherapy, and the difference was statistically significant ( t = -3.08, P = 0.030). The total effective rate of the experimental group was higher than that of the control group [85% (34/40) vs. 66.7% (26/39)], but the difference was not statistically significant ( χ2 = 4.96, P = 0.084). Karnofsky scores were (77±9) points and (77±12) points before and on day 21 after treatment in the experimental group, with no statistical difference ( t = -0.50, P = 0.623); Karnofsky scores were (78±10) points and (67±9) points in the control group, with statistical difference ( t = 8.32, P < 0.001). There was no statistical difference in Karnofsky score before treatment between the two groups ( t = 1.85, P = 0.068), but the experimental group was higher than the control group on day 21 after treatment ( t = 4.88, P < 0.001). The difference in the incidence of nausea and vomiting between the two groups was not statistically significant ( P > 0.05), and no chemotherapy-related hepatic, renal or cardiac adverse reactions were observed in either group. Conclusions:Combined therapy of traditional Chinese medicine could effectively prevent chemotherapy-related anemia and improve the quality of life of patients.

Role of the criteria based on preoperative serological indexes of AFP and GGT in predicting long-term survival of patients with hepatocellular carcinoma after liver transplantation / 器官移植

Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

Overexpression of Protein Phosphatase 2 Regulatory Subunit B"Alpha Promotes Glycolysis by Regulating Hexokinase 1 in Hepatocellular Carcinoma / 生物医学与环境科学（英文）

Objective@#To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC).@*Methods@#In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A.@*Results@#RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells.@*Conclusion@#Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.