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The morbidity and mortality of gastric cancer are high, while the overall therapeutic effect is poor without satisfactory. Clinical obstacles, such as low early-diagnosis rate, tumor heterogeneity, lack of accurate classification and precise treatment, therapeutic resistance, recurrence and metastasis, are the key point issues to the lower efficacy in treatment of gastric cancer. In order to solve these clinical problems, it is necessary to devote more energy to the basic research of gastric cancer, including tumor genomics; gene editing; tumor microenvironment; inflammation, aging and tumor; cell differentiation disorders; autophagy and cell death; metabolic disorders; immunotherapy and drug development. This paper will summarize the clinical obstacles in the treatment of gastric cancer, and describe the directions of basic research on these clinical problems in future, so as to provide notions for the translational research of gastric cancer.

Esophageal cancer (EC) is the seventh most common cancer worldwide. Patients with EC have a generally poor prognosis mainly due to the lack of effective treatments. Cancer immunotherapy is a promising novel treatment option for EC. This literature review investigated the clinical efficacy of immunotherapy either alone or in combination with chemotherapy or targeted therapy. In addition, we analyzed the adverse events associated with immune checkpoint inhibitors (ICIs). In conclusion, ICIs increase the efficacy of EC treatments, thereby improving the outcomes of EC patients. The findings of this study may help enhance the response to immunotherapy, diminish toxicity, and thus eventually improve medical care for patients with EC. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have shown that immune checkpoint inhibitors can improve the survival of patients with advanced non‐small cell lung cancer with KRAS mutations; however, there is a lack of comparisons between treatment regimens associated with immune checkpoint inhibitors, and our study aims to compare several treatment parties to find a more effective treatment regimen. Method: A comprehensive literature search was conducted across multiple databases, namely PubMed, Web of Science, Embase, and Cochrane Library, to identify relevant studies. The screened studies were thoroughly examined, and data were collected to establish a Bayesian framework. The study focused on two primary endpoints: overall survival (OS) and progression‐free survival (PFS). Data analysis and graphical plotting using R software and Revman (version 5.3). It is worth mentioning that the study protocol was registered with the International Prospective Registry for Systematic Reviews, ensuring transparency and adherence to predetermined protocols (CRD42022379595). Result: In total, our analysis included six RCTs involving 469 patients with KRAS mutations. Among these patients, 224 received chemotherapy, while 245 were treated with immune checkpoint inhibitors. Meta‐analysis results showed that the addition of ICIs could significantly improve OS and PFS (0.69, 95% CI 0.55, 0.86; 0.57, 95% CI 0.42, 0.77). The results of the network meta‐analysis showed that Pembrolizumab could improve OS (HR 0.42, 95% CI 0.22–0.80) and Pembrolizumab emerged as the most effective treatment option for enhancing OS in patients (SUCRA 65.03%). Additionally, pembrolizumab in combination with chemotherapy showed improvement in PFS (HR 0.47, 95% CI 0.29–0.76). Conclusion: Our analysis found that among advanced NSCLC patients with KRAS gene mutations, first‐line treatment with pembrolizumab alone demonstrated greater efficacy. Similarly, second‐line treatment with nivolumab alone was found to be more effective in this patient population. However, the sample size of this study was limited, Therefore, additional clinical data is necessary to validate this finding in subsequent research. [ABSTRACT FROM AUTHOR]

This study aims to investigate the mechanisms through which fructose diphosphate (FDP) causes anti-hypoxia and anti-fatigue effects and improves learning and memory. Mice were divided into three groups: low-dose FDP (FDP-L), high-dose FDP (FDP-H), and a control group. Acute toxic hypoxia induced by carbon monoxide, sodium nitrite, and potassium cyanide and acute cerebral ischemic hypoxia were used to investigate the anti-hypoxia ability of FDP. The tests of rod-rotating, mouse tail suspension, and swimming endurance were used to explore the anti-fatigue effects of FDP. The Morris water maze experiment was used to determine the impact of FDP on learning and memory ability. Poisoning-induced hypoxic tests showed that mouse survival time was significantly prolonged in the FDP-L and FDP-H groups compared with the control group (p < 0.05). In the exhaustive swimming test, FDP significantly shortened struggling time and prolonged the time of mass-loaded swimming; the rod-rotating test showed that endurance time was significantly prolonged by using FDP (p < 0.05). FDP significantly decreased lactate and urea nitrogen levels and increased hepatic and muscle glycogen and glucose transporter-4 and [Na.sup.+]-[K.sup.+]-ATPase (p < 0.05). To conclude, FDP enhances hypoxia tolerance and fatigue resistance and improves learning and memory ability through regulating glucose and energy metabolism. Key words: fatigue resistance, fructose diphosphate, glucose metabolism, hypoxia tolerance, learning and memory ability. Cette etude porte sur les modes d'action par lesquels le diphosphate de fructose (DPF) entraine des effets anti-hypoxie et anti-fatigue, et ameliore l'apprentissage et la memoire. Nous avons reparti des souris dans les trois groupes suivants : DPF-A, DPF-M et temoin. Nous avons etudie la capacite anti-hypoxie du DPF en creant une hypoxie toxique aigue a l'aide de monoxyde de carbone, de nitrite de sodium et de cyanure de potassium, ainsi qu'une hypoxie cerebrale ischemique aigue. Nous avons etudie les effets anti-fatigues du DPF a l'aide des tests de la tige rotative, de suspension caudale et d'endurance a la nage. Nous avons etabli l'incidence du DPF sur l'apprentissage et les capacites mnesiques a l'aide de l'experience du labyrinthe aquatique de Morris. Les tests d'hypoxie engendree par un empoisonnement ont montre que le temps de survie augmentait nettement dans les groupes DPF-A et DPF-M par rapport aux temoins (p < 0,05). Dans le test de nage jusqu'a l'epuisement, le DPF entrainait une abreviation notable du temps de lutte avec un prolongement du temps de nage avec charge; le test de la tige rotative a montre que le temps d'endurance augmentait de facon marquee avec l'utilisation de DPF (p < 0,05). Le DPF entrainait une diminution importante des taux de lactate et d'azote ureique, avec une augmentation des taux de glycogene hepatique et musculaire, ainsi que du transporteur du glucose 4 et de la [Na.sup.+]-[K.sup.+]-ATPase (p < 0,05). Pour conclure, le DPF permet d'ameliorer la tolerance a l'hypoxie et la resistance a la fatigue, ainsi que d'ameliorer l'apprentissage et les capacites mnesiques par l'intermediaire de la regulation du metabolisme energetique et du glucose. [Traduit par la Redaction] Mots-cles: resistance a la fatigue, diphosphate de fructose, metabolisme du glucose, tolerance a l'hypoxie, apprentissage et capacites mnesiques., Introduction Chronic hypoxia can cause inadequate oxygen supply to various organs, which inhibits oxidation and promotes glycolysis in different tissues, resulting in insufficient adenosine triphosphate (ATP) generation. Some vital organ [...]

Abstract.: It has been known that oxidative stress plays an important role in the development of diabetic nephropathy (DN). The antioxidative effects of Astragalus saponin I (AS I) were studied in vitro and in vivo. In the presence of high glucose and H2O2, the total antioxidative capability, catalase, reduced glutathione, and superoxide dismutase level of rat mesangial cells were significantly decreased, and transforming growth factor β1 (TGF-β1) mRNA level, collagen IV, and laminin level were significantly increased. When compared with those in the high glucose group, these 4 indexes of cells incubated in 2.0 and/or 20 µmol/L of AS I were significantly enhanced, and levels of TGF-β1 mRNA, collagen IV and laminin were statistically decreased. By flowcytomery, percentages of S phase of cells incubated in high glucose and H2O2 were lowered, while those in AS I were increased. Furthermore, the physical behaviors of rats treated with 12 mg/kg of AS I restored with vigor and weight gaining, while the level of HbAlC was significantly reduced. Thus, AS I has antioxidative effects and is a potential compound worth further study because it may prevent the development of DN. Keywords:: Astragalus saponin I, diabetic nephropathy, antioxidative, mesangial cell

Abstract: Astragaloside IV (AGS-IV), a new glycoside of cycloartane-type triterpene isolated from the root of Astragalus membranaceus (Fisch.) Bunge, has been used experimentally for its potent immune-stimulating, anti-inflammatory, and antioxidative [...]

Background: Traditional chemotherapy and molecular targeted therapy have shown modest effects on the survival of patients with pancreatic cancer. The current study aimed to investigate the antitumor effects of apatinib, Astragalus polysaccharide (APS), and the combination of both the drugs in pancreatic cancer cells and further explore the molecular mechanisms in vitro. Materials and methods: Expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in human pancreatic cancer cell lines ASPC-1, PANC-1, and SW1990 was detected by Western blotting. Cell proliferation was measured by MTS, and migration and invasion were detected by wound-healing and Transwell assays, respectively. Cell apoptosis rate was determined by flow cytometry and cellular autophagy level affected by apatinib, and APS was analyzed by Western blotting. Results: Human pancreatic cancer cell lines ASPC-1 and PANC-1 expressed VEGFR-2, but VEGFR-2 was not detected in SW1990. Either apatinib or APS inhibited cell proliferation in a dose-dependent manner in ASPC-1 and PANC-1. APS in combination with apatinib showed enhanced inhibitory effects on cell migration and invasion compared with apatinib monotherapy in ASPC-1 and PANC-1. Meanwhile, APS combined with apatinib strongly increased cell apoptosis percentage. Western blotting showed that the combination of APS and apatinib significantly enhanced the downregulation of phosphorylated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) (p-AKT and p-ERK) as well as matrix metalloproteinases-9 (MMP-9) expression. In addition, both apatinib and APS induced cellular autophagy. However, the expression of autophagy-related proteins was not further elevated in the combination group. Conclusion: The study first demonstrated that apatinib showed potentially inhibitory effects in pancreatic cancer cells and that APS enhanced the antitumor effects of apatinib through further downregulating the expression of phosphorylation of AKT and ERK as well as MMP-9. [ABSTRACT FROM AUTHOR]

In the process of network-based data flow transmission for various applications of information services, there are some problems, such as limited bandwidth and unclear priority level of business data, which affect the end-to-end reliable transmission efficiency because the system cannot perceive the link state. Traditional parallel link redundancy schemes have not fundamentally solved the problems of invulnerability and reliability. On the basis of sorting out the demand of service data flow transmission, this paper proposes a performance verification method of data flow packet scheduling algorithm based on QoS to solve the problems of network delay and congestion, and explores a reliable end-to-end service data flow transmission mode. [ABSTRACT FROM AUTHOR]

In this work, we used the Direct Laser Writing Grayscale Photolithography technology to fabricate a normally-off p-GaN gate high-electron-mobility transistor with the air-bridge source-connection. The air-bridge source-connection was formed using the Direct Laser Writing Grayscale Photolithography, and it directly connected the two adjacent sources and spanned the gate and drain of the multi-finger p-GaN gate device, which featured the advantages of stable self-support and large-span capabilities. Verified by the experiments, the fabricated air-bridge p-GaN gate devices utilizing the Direct Laser Writing Grayscale Photolithography presented an on-resistance of 36 Ω∙mm, a threshold voltage of 1.8 V, a maximum drain current of 240 mA/mm, and a breakdown voltage of 715 V. The results provide beneficial design guidance for realizing large gate-width p-GaN gate high-electron-mobility transistor devices. [ABSTRACT FROM AUTHOR]

Network Function Virtualization (NFV) offers service delivery flexibility and reduces overall costs by running service function chains (SFCs) on commodity servers with many cores. Existing solutions for placing SFCs in one server treat all CPU cores as equal and allocate isolated CPU cores to network functions (NFs). However, advanced servers often adopt Non-Uniform Memory Access (NUMA) architecture to improve the scalability of many-core systems. CPU cores are grouped into nodes, incurring performance degradation due to cross-node memory access and intra-node resource contention. Our evaluation shows that randomly selecting cores to place NFs in an SFC could suffer from 39.2 percent lower throughput comparing to an optimal placement solution. In this article, we propose Octans, an NFV orchestrator to achieve maximum aggregate throughput of all SFCs in many-core systems. Octans first formulates the optimization problem as a Non-Linear Integer Programming (NLIP) Model. Then we identify the key factor for problem solving as evaluating the throughput drop of an NF caused by other NFs in the same SFC or different SFCs, i.e., performance drop index, and propose a formal and accurate prediction model based on system level performance metrics. Finally, we propose two online algorithms to quickly find near-optimal placement solutions for one-time and incremental deployment. Extensive evaluation on a prototype implementation shows that Octans significantly improves the aggregate throughput comparing to two state-of-the-art placement solutions by 27.1 $\sim$ ∼ 45.2 percent for one-time deployment and by 20.9 $\sim$ ∼ 38.1 percent for incremental deployment, with very low prediction errors. Moreover, Octans could quickly find a near-optimal placement solution with tiny optimality gap. [ABSTRACT FROM AUTHOR]

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