12 research outputs found

    Molecular targets associated with ulcerative colitis and the benefits of atractylenolides-based therapy

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    Ulcerative colitis (UC) is a chronic inflammatory disease of the intestines that can significantly impact quality of life and lead to various complications. Currently, 5-aminosalicylic acid derivatives, corticosteroids, immunosuppressants, and biologics are the major treatment strategies for UC, but their limitations have raised concerns. Atractylenolides (ATs), sesquiterpene metabolites found in Atractylodes macrocephala Koidz., have shown promising effects in treating UC by exerting immune barrier modulation, alleviating oxidative stress, gut microbiota regulation, improving mitochondrial dysfunction and repairing the intestinal barrier. Furthermore, ATs have been shown to possess remarkable anti-fibrosis, anti-thrombus, anti-angiogenesis and anti-cancer. These findings suggest that ATs hold important potential in treating UC and its complications. Therefore, this review systematically summarizes the efficacy and potential mechanisms of ATs in treating UC and its complications, providing the latest insights for further research and clinical applications

    Mastering Complex Control in MOBA Games with Deep Reinforcement Learning

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    We study the reinforcement learning problem of complex action control in the Multi-player Online Battle Arena (MOBA) 1v1 games. This problem involves far more complicated state and action spaces than those of traditional 1v1 games, such as Go and Atari series, which makes it very difficult to search any policies with human-level performance. In this paper, we present a deep reinforcement learning framework to tackle this problem from the perspectives of both system and algorithm. Our system is of low coupling and high scalability, which enables efficient explorations at large scale. Our algorithm includes several novel strategies, including control dependency decoupling, action mask, target attention, and dual-clip PPO, with which our proposed actor-critic network can be effectively trained in our system. Tested on the MOBA game Honor of Kings, our AI agent, called Tencent Solo, can defeat top professional human players in full 1v1 games.Comment: AAAI 202

    The efficacy and safety of Xuefu Zhuyu Decoction Combined Mifepristone in the treatment of Uterine leiomyoma:A protocol systematic review and meta-analysis

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    Abstract Background Uterine leiomyoma (UL) is a common severe gynecological issue. In China, Xuefu Zhuyu Decoction (XFZYD), combined with Mifepristone, is widely used in the treatment of UL. However, their combined effectiveness and safety for this purpose have not yet been explored. Objective This systematic review aims to evaluate the effectiveness and safety of XFZYD combined with Mifepristone as a method of treatment for UL. Methods We searched the following 7 databases: 3 English medical databases (PubMed, EMBASE, Cochrane Library), and 4 Chinese medical databases (Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and the Wanfang database). The primary outcome was the effect of XFZYD combined with Mifepristone on the effective rate, uterine leiomyoma volume (ULV), and uterine volume (UV) of uterine leiomyoma. Bias risk was assessed using the Cochrane risk of bias tool. The software RevMan5 was used to evaluate the quality of the included studies and process the data. Results: This study will evaluate the efficacy and safety of XFZYD combined with Mifepristone in the treatment of uterine fibroids by evaluating the effective rate, Uterine Leiomyoma volume, and uterine volume, the incidence of estradiol, luteinizing hormone, and other indicators. Conclusion: This study will provide reliable evidence-based evidence for Xuefu Zhuyu Decoction Combined with Mifepristone in the treatment of uterine fibroids

    A magnetic torque optimization method for a hydraulic – magnetic coupling-drive cuttings cleaning tool

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    During the drilling process, cuttings carrying in the horizontal well section is relatively difficult, and cuttings beds form easily. A new type of hydraulic – magnetic coupling transmission cuttings cleaning tool is proposed, but the magnetic torque transmission influence mechanism, the optimal magnetic circuit structure and the magnet configuration are still yet to be studied. To this end, the finite element numerical simulation method is applied to analyze the influence of magnetic circuit structure and permanent magnet geometry on magnetic torque. The results of numerical simulation and laboratory experiments show that (1) the magnetic torque transmission efficiency can be improved by increasing the air gap flux density, reducing the magnetic reluctance and increasing the magnetostatic energy accumulation; (2) the magnetic torque increases first and then decreases as the number of pole-pair increases. The magnetic torque of 12 pairs of pole pairs reaches the maximum value; (3) by the coupling of the amount of magnets under the constraints of the effective section magnet coverage area percentage and the thickness of the magnet, it is obtained that when the thickness of the permanent magnet is 8.4 mm and the magnet coverage area percentage on the effective section of the tool is 71%, the maximum magnetic torque is generated per unit volume of magnet; (4) the absolute error of the indoor experimental result and the numerical simulation result is less than 17%, which can meet the engineering calculation accuracy requirements. It is concluded that the established numerical simulation model is reasonable and can be used as a technical means for the optimization analysis of the tool structure. Keywords: Horizontal drilling, Cuttings, Cleaning tool, Hydraulic – magnetic coupling, Permanent magnet, Magnetic torque, Magnetic flux density, Numerical optimizatio

    Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism

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    Breast cancer (BC) is a serious global challenge, and depression is one of the risk factors and comorbidities of BC. Recently, the research on the comorbidity of BC and depression has focused on the dysfunction of the hypothalamic–pituitary–adrenal axis and the persistent stimulation of the inflammatory response. However, the further mechanisms for comorbidity remain unclear. Epoxide metabolism has been shown to have a regulatory function in the comorbid mechanism with scattered reports. Hence, this article reviews the role of epoxide metabolism in depression and BC. The comprehensive review discloses the imbalance in epoxide metabolism and its downstream effect shared by BC and depression, including overexpression of inflammation, upregulation of toxic diols, and disturbed lipid metabolism. These downstream effects are mainly involved in the construction of the breast malignancy microenvironment through liver regulation. This finding provides new clues on the mechanism of BC and depression comorbidity, suggesting in particular a potential relationship between the liver and BC, and provides potential evidence of comorbidity for subsequent studies on the pathological mechanism

    Prognostic Value of Negative Emotions on the Incidence of Breast Cancer: A Systematic Review and Meta-Analysis of 129,621 Patients with Breast Cancer

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    Breast cancer (BC) is one of the common malignant tumors in women and affects 1.6 million new cases globally each year. Investigators have recently found that negative emotions (NEs) and their impacts have greatly influenced the incidence and risk of BC. The present study aims to provide an association between NEs and the incidence of BC with possible risk factors. A total of 9343 studies were screened; nine studies met all inclusion criteria that were considered for the meta-analysis. The qualitative studies were measured by the Newcastle-Ottawa Scale; the observational studies were included with relative risks (RR) and corresponding 95% confidence intervals (CI). Besides the NEs and BC, the possible risk factors were evaluated. We analyzed data from 129,621 women diagnosed with NEs of which 2080 women were diagnosed with BC and their follow-up year ranges were from 4–24 years. NEs were significantly (p < 0.0001) associated with a higher incidence of BC with RR = 1.59, 95% CI:1.15–2.19, with other high-risk factors including, geographical distribution, emotion types, standard diagnosis of NEs, and follow-up duration. This study suggests that NEs significantly increase the risk for the incidence of BC, which can be supportive of the prognosis of the disease

    DataSheet1_The zhuyu pill relieves rat cholestasis by regulating the mRNA expression of lipid and bile metabolism associated genes.DOCX

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    Background: The Zhuyu pill (ZYP), composed of Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, is an effective traditional Chinese medicine with potential anti-cholestatic effects. However, the underlying mechanisms of ZYP remain unknown.Objective: To investigate the mechanism underlying the interventional effect of ZYP on mRNA-seq analysis in cholestasis rat models.Materials and methods: This study tested the effects of a low-dose (0.6 g/kg) and high-dose (1.2 g/kg) of ZYP on a cholestasis rat model induced by α-naphthyl-isothiocyanate (ANIT, 50 mg/kg). Serum biochemistry and histopathology results were used to evaluate the therapeutic effect of ZYP, and mRNA-Seq analysis was performed and verified using real-time fluorescence quantitative PCR (qRT-PCR). GO, KEGG, and GSEA analyses were integrated to identify the mechanism by which ZYP impacted cholestatic rats.Results: ZYP was shown to significantly improve abnormal changes in the biochemical blood indexes and liver histopathology of cholestasis rats and regulate pathways related to bile and lipid metabolism, including fatty acid metabolism, retinol metabolism, and steroid hormone biosynthesis, to alleviate inflammation, cholestasis, and lipid metabolism disorders. Relative expression of the essential genes Cyp2a1, Ephx2, Acox2, Cyp1a2, Cyp2c11, and Sult2a1 was verified by qRT-PCR and showed the same trend as mRNA-seq analysis.Conclusion: ZYP has a significant anti-cholestatic effect by regulating bile metabolism and lipid metabolism related pathways. These findings indicate that ZYP is a novel and promising prospect for treating cholestasis.</p
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