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Document-level relation extraction is a challenging task in information extraction, as it involves identifying semantic relations between entities that are dispersed throughout a document. Existing graph-based approaches often rely on simplistic methods to construct text graphs, which do not provide enough lexical and semantic information to accurately predict the relations between entity pairs. In this paper, we introduce a document-level relation extraction method called SKAMRR (Sememe Knowledge-enhanced Abstract Meaning Representation and Reasoning). First, we generate document-level abstract meaning representation graphs using rules and acquire entity nodes’ features through sufficient information propagation. Next, we construct inference graphs for entity pairs and utilize graph neural networks to obtain their representations for relation classification. Additionally, we propose the global adaptive loss to address the issue of long-tailed data. We conduct extensive experiments on four datasets DocRE, CDR, GDA, and HacRED. Our model achieves competitive results and its performance outperforms previous state-of-the-art methods on four datasets.

The charge prediction task aims to predict appropriate charges for a given legal case automatically, which still confronts some challenging problems such as performance improvement and confusing charges issue. In this paper, inspired by the impressive success of deep neural networks in legal intelligence field, we present an end-to-end framework named law article deduplication attention neural network, ADAN, to address these problems. The incorporation of hierarchical sequence encoder and attention mechanism is employed to learn better semantic representations of fact description texts. To distinguish confusing charges, we use the relevant law articles of a given case as auxiliary information, and propose a novel difference aggregation mechanism among similar law articles for extracting effective distinguishable features. The experimental results on real-world datasets show that the performance of our proposed model is significantly better than existing methods on all evaluation metrics.

Objective To study the expression and clinical significance of keratinocyte growth factor receptor (KGFR) and tissue factor pathway inhibitor-2 (TFPI-2) in cervical cancer tissues. Methods A retrospective analysis of 45 cervical cancer patients admitted to our hospital from January 2020 to December 2021 was used as the observation group, and 45 healthy cervical patients in our hospital during the same period were selected as the control group. The KGFR, TFPI- 2 Positive rate, pathological features and correlation with cervical cancer. result The positive rate of KGFR in the observation group was 0.00% lower than that in the control group (84.44%), and the positive rate of TFPI-2 was 100.00% higher than that in the control group ( 26.67 %) , P < 0.05. There were significant differences between KGFR positive and cervical cancer TNM stage and degree of differentiation; there were significant differences between TFPI-2 positive expression and cervical cancer TNM stage, degree of differentiation and lymph node metastasis , P P < 0.05. Conclusion The expression of KGFR is up-regulated and the expression of TFPI-2 is down-regulated in cervical cancer tissue. The expression levels of the two are directly related to the poor prognosis of cervical cancer patients , and there is a certain correlation with the incidence of cervical cancer .

The role of inulin in alleviating obesity-related disorders has been documented; yet, its underlying mechanisms still need to be further investigated. This study attempted to elucidate the causative link between the gut microbiota and the beneficial effect of inulin on obesity-related disorders via transferring the fecal microbiota from inulin-dosed mice to high-fat diet (HFD)-induced obese recipient mice. The results show that inulin supplementation can decrease body weight, fat accumulation, and systemic inflammation and can also enhance glucose metabolism in HFD-induced obese mice. Treatment with inulin reshaped the structure and composition of the gut microbiota in HFD-induced obese mice, as characterized by increases in the relative abundances of Bifidobacterium and Muribaculum and decreases in unidentified_Lachnospiraceae and Lachnoclostridium. In addition, we found that these favorable effects of inulin could be partially transferable by fecal microbiota transplantation, and Bifidobacterium and Muribaculum might be the key bacterial genera. Therefore, our results suggest that inulin ameliorates obesity-related disorders by targeting the gut microbiota.

Given an increasing number of children with ASD, the need for inclusive education has rapidly increased in China. Since 2011, children with ASD have been eligible for inclusive education. However, little is known of the implementation process by key personnel. The purpose of the current study was to qualitatively explore elementary school teachers' experiences and perspectives on an inclusive education policy and practice for students with ASD. Participants were from 5 elementary schools in 2 districts in Shanghai. This study consisted of data collection in 2 phases. First, semi-structured, in-depth interviews were conducted with school psychologists and vice principals responsible for students' mental health for implementation of general inclusive education at each school. Second, focus groups of frontline teachers were assembled to hear their firsthand experiences. A thematic analysis was performed. Findings indicated that although all 5 schools had some ASD-related support, training and resources varied depending on whether learning in regular classrooms (LRC) was implemented. Frontline teachers in particular faced challenges implementing LRC, including the limited extent of LRC, tedious implementation procedures, and parents' misconceptions of LRC. Regardless of these challenges, frontline teachers tried to support students with ASD as much as they could. The current findings should help to advance the inclusive education policy in Shanghai, including increasing the availability of inclusive education resources and training for teachers, issuing specific LRC guidance, and reducing ASD-related stigma. This study is among the first to explore the implementation of inclusive education in urban China.

ObjectiveGrowth hormone receptor (GHR) mediates most GH biological actions. This study is aimed to evaluate whether GHR fl/d3 polymorphism contributes to the inter-individual variability of growth and metabolism in healthy children and adolescents.MethodsA total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of GHR fl/d3 polymorphism with height, BMI, metabolic traits, and hypertension by estimating the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsGHR d3 allele was inversely associated with overweight, total cholesterol (TC) and triglyceride (TG) levels (OR [95% CI] for overweight: 0.754 [0.593-0.959], P = 0.021; OR [95% CI] for TC: 0.744 [0.614-0.902], P = 0.003; OR [95% CI] for TG: 0.812 [0.654-0.998], P = 0.047). GHR d3 allele was associated with decreased odds of pre-hypertension in boys (OR [95% CI]: 0.791 [0.645-0.971], P = 0.025), but associated with increased odds of pre-hypertension and hypertension in girls (ORs [95% CIs]: 1.379 [1.106-1.719], P = 0.004; OR [95% CI]: 1.240 [1.013-1.519], P = 0.037). Interaction of GHR fl/d3 polymorphism with gender contributed to increased odds of pre-hypertension and hypertension (interactive ORs [95% CIs]: 1.735 [1.214-2.481], P = 0.003; OR [95% CI]: 1.509 [1.092-2.086], P = 0.013). Stratification analysis showed that the correlation tendencies of GHR fl/d3 polymorphism and BMI with age were different between two cities with discrepant economic development levels.ConclusionGHR fl/d3 polymorphism is associated with growth, metabolism, and hypertension in children and adolescents with the gender specificity, and the genetic effect of GHR fl/d3 may be modified by the local socioeconomic levels.

Legal judgment prediction (LJP) is a crucial task in legal intelligence to predict charges, law articles and terms of penalties based on case fact description texts. Although existing methods perform well, they still have many shortcomings. First, the existing methods have significant limitations in understanding long documents, especially those based on RNNs and BERT. Secondly, the existing methods are not good at solving the problem of similar charges and do not fully and effectively integrate the information of law articles. To address the above problems, we propose a novel LJP method. Firstly, we improve the model’s comprehension of the whole document based on a graph neural network approach. Then, we design a graph attention network-based law article distinction extractor to distinguish similar law articles. Finally, we design a graph fusion method to fuse heterogeneous graphs of text and external knowledge (law article group distinction information). The experiments show that the method could effectively improve LJP performance. The experimental metrics are superior to the existing state of the art.

In this retrospective analysis, we aimed to analyze the epidemic characteristics of neonatal mortality due to preterm birth at 28–36 weeks gestation in different regions from 2009 to 2018. Data were obtained from China’s Under-5 Child Mortality Surveillance System (U5CMSS). The χ2 trend test, Poisson regression and the Cochran-Mantel-Haenszel method were used in this study. We found that 51.3%, 42.0% and 44.5% of neonate deaths were preterm infants, and immaturity was mainly attributed to 60.1%, 64.1% and 69.5% of these deaths, in the eastern, central and western regions, respectively. The preterm neonatal mortality rate due to immaturity dropped from 149.2, 216.5 and 339.5 in 2009 to 47.4, 83.8 and 170.1 per 100 000 live births in 2018, giving an average annual decline rate of 12.1%, 11.6% and 6.3% in the eastern, central and western regions, respectively, during the studying period. The relative risk of preterm neonatal mortality due to immaturity were 1.3 and 2.3 for the central regions and western regions in 2009–2010, ascending to 2.2 and 3.9 in 2017–2018. The proportion of preterm neonatal deaths with a gestational age

A pectin/chitosan matrix-loaded curcumin film (PCCF) with a deep eutectic solvent (DES) as the solvent and plasticizer was prepared in this study. Different quantities of curcumin (identified as PCCF-0, PCCF-1, PCCF-2. PCCF-3) were loaded on the pectin/chitosan film in order to evaluate their effects on the film properties. Results showed that curcumin could interact with the pectin/chitosan matrix and form a complex three-dimensional network structure. PCCF could promote the thickness, tensile strength, thermal properties, antioxidant and antiseptic capacities, but deteriorate the light transmission and elongation at the same time. The addition of curcumin would change the color of the film, without significantly affecting the moisture content. The tensile strength of PCCF-3 reached the maximum value of 3.75 MPa, while the elongation decreased to 10%. Meanwhile, the water-resistance properties of PCCF-3 were significantly promoted by 8.6% compared with that of PCCF-0. Furthermore, PCCF showed remarkable sustained antioxidant activities in a dose-dependent manner. PCCF-3 could inhibit DPPH and ABTS free radicals by 58.66% and 29.07%, respectively. It also showed antiseptic capacity on fresh pork during storage. Therefore, curcumin addition could improve the barrier, mechanical, antioxidant and antiseptic properties of the polysaccharide-based film and PCCF has the potential to be used as a new kind of food packaging material in the food industry.

Traditional Chinese medicine (TCM) has been used to treat diabetes for a long time, but its application has not been widely accepted due to unstandardized product quality and complex pharmacological mechanisms. The modernization of TCM is crucial for its further development, and in recent years the metabolomics technique has largely driven its modernization. This review focuses on the application of NMR-based metabolomics in diabetic therapy using TCM. We identified a series of metabolic pathways that altered significantly after TCM treatment, providing a better understanding of the metabolic mechanisms of TCM for diabetes care.

Growth hormone receptor (A total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.

Doxorubicin (DOX), a widely used anti-tumor drug, can give rise to severe cardiotoxicity by oxidative stress and cell apoptosis, which restricts its clinical application. α-Linolenic acid (ALA) has been shown to serve as a potent cardioprotective agent. The aim of this study was to explore the protective effects of ALA on DOX-induced cardiotoxicity and the underlying molecular mechanisms for this cardioprotection in rats. Rats were randomly divided into four groups and administrated with normal saline, ALA (500 µg/kg), DOX (2.5 mg/kg), or ALA (500 µg/kg) plus DOX (2.5 mg/kg) for 17 days. The results showed that DOX treatment significantly increased the heart weight/body weight, liver wet weight (WW)/dry weight (DW), lung WW/DW, serum levels of brain natriuretic peptide, creatine kinase-MB, lactate dehydrogenase, and cardiac troponin I, myocardial necrosis and myocardial malondialdehyde content, and induced the mRNA expression of Nrf2 in the nucleus, cleaved caspase-3, Bax, and superoxide dismutase (SOD). In addition, DOX led to a significant decrease in left ventricular end-diastolic volume, stroke volume, ejection fraction, SOD, glutathione-peroxidase, catalase, as well as the expression of Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm, phospho-AKT, phospho-ERK, and Bcl-2. Co-treatment with ALA significantly eliminated these changes induced by DOX except further reduction of Keap1 and elevation of Nrf2 and SOD mRNA. These results showed the cardioprotective effects of ALA on DOX-induced cardiotoxicity in rats. The mechanisms might be associated with the enhancement of antioxidant defense system through activating Keap1/Nrf2 pathway and anti-apoptosis through activating protein kinase B/extracellular signal regulated kinase pathway. Our results suggested a promising future of ALA-based preventions and therapies for myocardial damage after administration of DOX.

Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression pro-inflammatory transcription factors Nuclear transcription factor (NF)-κB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-κB and STAT3 activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective.

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.

BackgroundAC3 is one of adenylyl cyclase isoforms involved in cAMP and insulin signaling pathway. Recent reports have demonstrated that the AC3 genetic polymorphisms are associated with obesity in a Swedish population. AC3 knock out mice exhibit obese when they age. These findings suggest that AC3 plays an important role in the regulation of body weight.Methodology/principal findingsIn the present study, we evaluated the association between the AC3 genetic polymorphisms and obesity in a Han Chinese population. A total of 2580 adults, including 1490 lean (BMI = 18.5-23.9), 677 overweight (BMI 24.0-27.9) and 413 obese (BMI ≥28.0) subjects were genotyped for 5 TagSNPs in the AC3 gene. Single maker association analyses indicated that SNP rs753529 was significantly associated with BMI in obese subjects (P = 0.022, OR = 0.775 95%CI = 0.623-0.963), but not in overweight subjects (P = 0.818). Multiple maker association analyses showed that the haplotype (G-G-G) constructed with SNPs rs1127568, rs7604576 and rs753529 was significantly associated with obesity (P = 0.029). Further genotyping of SNP rs753529 in 816 children, including 361 overweight subjects (BMI>P(80)) and 455 controls (BMI = P(20-50)) were performed, and no significant association with BMI was found. All tests were adjusted for age, sex, physical activity index, household income and/or diet expenses.ConclusionsThe present study provides replication evidence that the AC3 genetic polymorphisms are associated with decreased risk of obesity among adults but not in children in a Chinese Han population. The data also suggest that the AC3 genetic effects on BMI may have interaction with the factors related to ageing and environment.

Abstract 5103 Despite recent treatment advances, multiple myeloma(MM) remains incurable. FTY720 has initially been used as an immunosuppressant and is promising in treating relapsing/remitting multiple sclerosis. FTY720 has also been studied in several hematological malignancies including MM, but there are no reports about autophagy induced by FTY720 in MM. Therefore, we assessed the efficacy of FTY720 on MM cell line U266 and investigated the associated mechanisms of cell death. First we examined whether or not FTY720 induce cell death in U266 cells. We treated U266 cells with different dosage of FTY720 and then cell viability was measured at 24 hours by CCK-8 assay. The results showed cell viability started to reduce at 5uM and reach to 15% at 20uM, suggesting FTY720 affects cell survival in MM cell line. We then measured cell viability at 2□ A6□ A24 hours at fix concentration of 20.0 mM, 50% cells were killed even at 2 hours as compared with control group. Cell apoptosis was also measured by flow cytometry(FCM). Apoptosis rate(%) increased in a dose-dependent manner after FTY720 treatment. The percent Annexin+/7AAD- cells in the control group remained constant 5% and 15% to 30% in the drug treated time course experiments. The cell viability and apoptosis induced by FTY720 showed a dose- and time-dependant manner. Z-VAD-fmk, a pancaspase inhibitor, could rescue cell death caused by FTY720 and exposure of U266 cells to different concentration of FTY720 induced cleavage of caspase-3. We conclude FTY720 can induce a caspase-dependent cell death in U266 cells. Mcl-1, survivin, bcl-2 and Bid are antiapoptotic proteins and degradation of these proteins are required for the induction of apoptosis. In our study, the expression of Mcl-1, survivin and bcl-2 were reduced after the treatment which confirmed FTY720 induced apoptosis by down-regulating the expression of antiapoptotic proteins. Consistent with this, cleavage of Bid was also increased after the FTY720 treatment. Autophagy is another cell death pathway characterized by intracellular degradation system that delivers cytoplasmic constitutions to the lysosome. Conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II is a marker of autophagosome degradation. We observed increasing amount of conversion from LC3-I to LC3-II after FTY720 treatment, suggesting that FTY720 could induce autophagy in U266 cells. This conversion is dose-dependent. Interestingly, LC3-II accumulated in the presence of Bafilomycin A1, an inhibitor of autophagosome-lysosome fusion and LC3-II degradation, in cells treated with FTY720, confirmed that autophagic flux was induced by FTY720. To understand the role of apoptosis and autophagy played in the FTY720 induced cell death, we examined cell viability and apoptosis after FTY720 treatment in the presence or absence of Bafilomycin A1. Cell viability was higher and apoptosis was lower in the presence of Bafilomycin A1 after FTY720 treatment, indicating that Bafilomycin A1 could rescue cell death and apoptosis caused by FTY720. The results suggested that autophagy and apoptosis synergized to induce MM cell death after FTY720 treatment. We found Bafilomycin A1 rescued FTY720 induced cell death is dependent on the accumulation of anti-apoptotic protein Mcl-1 and survivin, it is possible that autophagy helps to degrade the anti-apoptotic proteins in the lysosome and synergize the cell death induced by FTY720. To investigate the mediators of FTY720-induced apoptosis and autophagy, we examined reactive oxygen species (ROS), which plays an important role in regulating both apoptosis and autophagy. Potential antioxidants N-acetyl-L-cysteine (NAC) and Tiron both could rescue apoptosis induced by FTY720, suggesting that FTY720 induced apoptosis via the activation of ROS. Furthermore, both NAC and Tiron blocked the conversion of LC3-I to LC3-II, indicating that FTY720 leads to ROS production, which results in autophagosome development and autolysosomal degradation. These studies indicate autophagy induced by FTY720 contributes to cell death in U266 cells and suggest that the function of FTY720 maybe can benefit from autophagy enhancement. To this regard, the ability of FTY720 to induce autophagy-dependent cell death in U266 cells, if confirmed in vivo, may represent a relatively selective therapy for the treatment of MM. Disclosures: No relevant conflicts of interest to declare.