Objective:To investigate the relationship between previous bleeding history and poor prognosis of patients with acute upper gastrointestinal bleeding.Methods:This study was a prospective multicentre real-world study (Acute Upper Gastrointestinal Real-word study, AUGUR study). The data of patients with UGIB who were admitted to the emergency department of 20 tertiary hospitals in China from June 30, 2020 to February 10, 2021 were collected. According to the number of previous bleeding history, the patients were divided into three groups (0 time, 1-3 times, and≥4 times). Based on the patient’s demographic data, clinical characteristics, laboratory data, treatment, and outcomes, univariate and logistic regression analysis were performed to investigate the correlation between the number of previous bleeding and the 90-day mortality and rebleeding of patients with gastrointestinal bleeding.Results:A total of 1 072 patients with acute UGIB were included in this study. The all-cause mortality and rebleeding rate of all patients were 10.9% (117/1 072) and 11.8% (129/1 072), respectively. Among them, 712 patients (66.42%) had no previous bleeding, 297 patients (27.71%) had previous bleeding 1-3 times, and 63 patients (5.88%) had previous bleeding≥4 times. In univariate analysis, age, vital signs and consciousness on admission, history of liver cirrhosis, onset with hematemesis, admission hemoglobin, varicose veins bleeding, peptic ulcer bleeding, red blood cell infusion, tracheal intubation and the use of vasopressors after admission were risk factors for the 90-day mortality and rebleeding rate. Multivariate logistic regression analysis showed that patients with previous bleeding≥4 times had a higher risk of the 90-day mortality ( OR=2.17, 95% CI: 1.04-4.57, P=0.040) and rebleeding ( OR=2.32, 95% CI: 1.19-4.53, P=0.013). Conclusions:The history of previous bleeding≥ 4 times can be used as an independent risk factor for the 90-day mortality and rebleeding in patients with acute UGIB.

Objective:To determine the effect of hypoxic stress on glioma cell XBP1 expression, the relationship between XBP1 expres-sion and sugar metabolism, the influence of XBP1 repression on the survival rate of glioma cells under normoxia and hypoxia, and the influence of XBP1 on glioma cell glycolysis. Methods:We tested XBP1 activation in human glioma cell lines cultured under normoxia and hypoxia. XBP1 expression was repressed with siRNA technology. Cells were treated with oxidative phosphorylation inhibitor. We then detected the variation in cell apoptosis, sugar metabolism mode, and cell apoptosis and glycolysis products under normoxia and hypoxia. Results:XBP1 activation increased under hypoxia. Silencing XBP1 expression reduced glioma cell survival level, ATP and lactic acid production, and glucose consumption under hypoxia. After inhibiting cell oxidative phosphorylation, XBP1 repression significantly reduced the survival level of glioma cells. Conclusion:Hypoxia can activate XBP1 in glioma cells. Under hypoxia, XBP1 silencing de-presses cell activity and glycolysis. Glycolysis of glioma cells under hypoxia depends on XBP1 activation.

Pineapple (Ananas comosus) leaves contain mainly phenolic components with antioxidant and hypolipidemic effects. One of the principle components is p-coumaric acid. In this study, the transport behavior of p-coumaric acid, was observed after the administration of pineapple leaf phenols in vitro. Simultaneously, the effect of the phenols on glucose, total cholesterol and triglycerides transportation and metabolism in HepG2 cells was also observed. The results showed that the phenols had good transport characteristics. 5 min after the administration, p-coumaric acid of the phenols could be detected, and the content of p-coumaric acid reached the peak concentration after 60 min of the administration. p-coumaric acid of phenols have time-and dose-dependent manner. While promoting glucose transporter (GLUT4) and low density lipoprotein receptor (LDLR) expression, the phenols decreased intracellular lipid content. This reduction of intracellular lipid content was highly correlated with the promotion of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) expression, while the reduction of intracellular glucose levels was correlated with glycogen synthesis in the cells.
Ananas ; chemistry ; Biological Transport ; drug effects ; Cholesterol ; metabolism ; Glucose ; metabolism ; Hep G2 Cells ; Humans ; Lipid Metabolism ; drug effects ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry

Activation pattern recognition receptors can cause the startup of downstream signaling pathways, the expression of inflammatory factors, and finally immunological inflammatory reaction. Either exogenous pathogenic microorganisms or endogenous tissue components can activate these pattern recognition receptors as ligands at varying degrees, and then cause the immunological inflammatory reaction. Therefore, it is of great significance to inhibit relevant receptors, as well as the immunological inflammatory reaction, in order to avoid tissue injury during the course of disease. Baicalin is able to specifically inhibit the expression of TLR2/4-NOD2, inhibit the expression of inflammatory factors IL-1beta, IL-6 and TNF-alpha, and thereby reducing the injury of the tissue cells during the course of disease. This effect is non-specific with tissues, which is of great theoretical and practical significance in druggability. In addition, the drug metabolism and toxicity of baicalin are also discussed for its druggability in this article.
Animals ; Flavonoids ; pharmacology ; Humans ; Nod2 Signaling Adaptor Protein ; metabolism ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 4 ; metabolism

AIM: Euphorbia kansui (E. KS) is a traditional medicine used in China for thousands of years with the effect of propulsion in the gastrointestines. However, there is no reported study of E. KS on gastrointestinal motility until now. The aim of this work is to study the effect of E. KS on the propulsion of gastrointestines, and to elucidate the possible mechanism of action. METHODS: E.KS was prepared as a 30% ethanol extract and used for the experiment of small and large intestines of mice by oral administration with three different dosages (1.2, 0.6 and 0.3 g·kg(-1)). The feces were observed in vivo. The morphology was carried out to detect if there are any changes in the intestines after the extract of E. KS administration. The assays of mRNA and protein expression were employed to observe IL-1β, TNFα and caspase 3. RESULTS: It was shown that the extract of E.KS promoted diarrhea in mouse feces after administration, inhibited the contraction of smooth muscle of mouse small intestine and caused the inflammatory exudation on the mucosa of the intestines, enhanced the expression of both mRNA and the protein levels of IL-1β and TNFα in the small or large intestines. CONCLUSION The results showed that the extract of E. KS acted on the intestinal smooth muscle with propulsion of feces involving the irritation of the intestines with acute inflammatory reactions.
Animals ; Diarrhea ; etiology ; genetics ; immunology ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Euphorbia ; adverse effects ; chemistry ; Female ; Gastrointestinal Motility ; drug effects ; Humans ; Interleukin-1beta ; genetics ; immunology ; Intestines ; drug effects ; physiopathology ; Male ; Mice ; Mice, Inbred ICR ; Muscle, Smooth ; drug effects ; physiopathology ; Plant Roots ; adverse effects ; chemistry ; Tumor Necrosis Factor-alpha ; genetics ; immunology

BACKGROUNDBaicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke. Most of the studies of Toll-like receptor 2/4 (TLR2/4) during cerebral ischemia had defined their specific expressions in microglia in hippocampus tissue. To explore the targets of baicalin in stroke, we detected the expressions of TLR2/4 in vitro/vivo.

METHODSBy constructing a cerebral ischemia-reperfusion model in vivo and glucose oxygen deprivation model, we successfully induced neuron damage, then added baicalin and detected expressions of TLR2/4, nuclear factor-kB (NF-kB), tumor necrosis factor-alpha (TNFα), and interleukin-1β (IL-1β) in mRNA level and protein level.

RESULTSWe found distinct upregulations of TLR2/4 and TNFα in both mRNA level and protein level in PC12 cells and primary neurons. Moreover, TLR2/4 and TNFα expressions were significantly higher in mice hippocampus treated with cerebral ischemia-reperfusion. Baicalin could downregulate the expressions of TLR2/4 and TNFα in the damaged cells and mice hippocampus effectively.

CONCLUSIONSNeurons could respond to the damage and activate the related signal pathway directly. TLR2/4 responsed to the damage and sent the signal to downstream factor TNFα through activating NF-kB. Baicalin could inhibit the inflammatory reaction in neuron damage and TLR might be its targets, which explained why baicalin could widely be used in the clinical treatment of stroke.

Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; Cells, Cultured ; Female ; Flavonoids ; therapeutic use ; Interleukin-1beta ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; NF-kappa B ; genetics ; metabolism ; Neurons ; drug effects ; metabolism ; PC12 Cells ; Rats ; Reperfusion Injury ; drug therapy ; genetics ; metabolism ; Toll-Like Receptor 2 ; genetics ; metabolism ; Toll-Like Receptor 4 ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

Tumor rapid growth depends on neovascularization. Vascular endothelial growth factor, the main mediator during the occurrence and formation of vascularization, has specific receptors whose expression rate shows difference of orders of magnitude between tumor and the normal tissue, so it can be used to transport toxin molecules to the proliferative tumor endothelial and kill cancer cells. In our experiment, we constructed fusion protein DT-VEGF by linking diphtheria toxin's forward 389 amino acids's gene and VEGF165 via a linker. DT-VEGF is expressed in E. coli and purified. Our experiment proves in can kill vascular endothelial cells specifically, and the inhibition of neovascularization of chicken chorionic membrane is also confirmed.
Angiogenesis Inhibitors ; biosynthesis ; Diphtheria Toxin ; biosynthesis ; genetics ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; Humans ; Immunotoxins ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Vascular Endothelial Growth Factors ; biosynthesis ; genetics

Wandaitang, which is one of classical traditional Chinese medicine(TCM) prescriptions, is derived from Collected Exegesis of Recipes of Fu Qingzhu' s Obstetrics and Gynecology. It is commonly used in modern clinical practice, and included in the Catalogue of Ancient Classical Prescriptions (The First Batch). Collected Exegesis of Recipes of Fu Qingzhu' s Obstetrics and Gynecology and Chen Shi-duo' s Bianzhenglu have a complicated relationship. Both of them have another biography, named Nvke Xianfang and Bianzheng Qiwen. The composition of Wandaitang in the four books is slightly different, while the prescription's explanations and other records are almost the same. The research and development of Wandaitang should be based on the records of Collected Exegesis of Recipes of Fu Qingzhu's Obstetrics and Gynecology. Compared with other classical literatures, Collected Exegesis of Recipes of Fu Qingzhu's Obstetrics and Gynecology was published in a late period and less reproduced in other ancient books. To study the function of Wandaitang, we need to analyze the records in the original book. In addition, we need to make a multi-angle analysis by reference to the theory of TCM, the composition of drugs, the significance of compatibility, as well as the understanding of modern famous doctors, clinical reports and experimental studies in all aspects. The study found that the functions of Wandaitang were relatively concentrated, but with wide major functions involving internal medicine, surgery, gynecological, pediatric, andrological and other departments. According to the study, the authors believe that the functions of the classical TCM prescription of Wandaitang are invigorating spleen to eliminate dampness, dispersing the liver and rectifying Qi, and invigorating Yang. It can be used to treat leucorrhea, diarrhea, edema and stranguria with the syndromes of pale, languid, little food, loose stool and depression. Wandaitang can also be used to treat vaginitis, cervicitis, pelvic inflammatory disease, irritable bowel syndrome, chronic colitis, chronic nephritis, nephrotic syndrome and chronic prostatitis.

The aim of this study was to analyze the anti-cancer effect and mechanism of action of the flavonoids of Astragalus membranaceus (TFA) when combined with cisplatin on Lewis lung carcinoma-bearing mice. This animal experiment was approved by the Committee of the Ethics of Animal Experiment of Shanxi University (SXULL2018012). Pharmacological indices such as tumor weight, tumor volume growth curves, inhibition rate and organ indices showed that the TFA could reduce toxicity and enhance the efficacy of cisplatin. The target of TFA was predicted by network pharmacology analysis and the result showed that calycosin-7-O-β-D-glucoside might be the main active compound responsible for the anticancer effect of TFA. TRP53 (cellular tumor antigen p53), RAC1 (Ras-related C3 botulinum toxin substrate 1), ERBB2 (receptor tyrosine-protein kinase erbB-2), VEGFA (vascular endothelial growth factor A) and STAT3 (signal transducer and activator of transcription 3) may be associated with TFA in enhancing efficacy and reducing the toxicity of cisplatin. The IL-6 content in serum and expression levels of STAT3 and p53 in tumor tissues suggested that TFA may inhibit tumor growth through the IL-6/STAT3 pathway; UPLC-MS-based serum metabolomic analysis suggested that the metabolic pathways related to lung cancer include sphingolipid metabolism, retinol metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis, and the TFA-regulated corresponding pathway of bile acid biosynthesis. In this study, the anti-cancer effect and mechanism of action of TFA combined with cisplatin on Lewis lung carcinoma-bearing mice was analyzed by the combination of various techniques, which lay a foundation for further development of anticancer drugs.

A variety of pharmacological effects of berberine (BBR) are constantly being discovered with the deepening of BBR research. What followed is how to rationally use the drug according to these new pharmacological effects. Because of some cardiac toxicity and poor oral absorption, conflicts may arise between improving the bioavailability and controlling the toxicity of BBR. Meanwhile some new therapeutic uses of BBR, such as hypolipidemia, hypoglycemia as well as prevention and treatment of neurodegenerative diseases, need long-termoral administration, thereby may lead to alteration of intestinal flora and potentially affect body's other physiological functions. Based on the stated targets of BBR and related pharmaceutical properties, comprehensive analysis of these issues was conducted in this study. Some suggestions were presented below：the effect of long-term oral administration on body function, especially the intestinal flora, needs to be further investigated; risks shall be considered in changing the composition of the formulation to improve the absorption rate of oral administration; for the medication with higher concentration demand (such as anti-cancer), targeted drug-delivery is worthy to be considered.