OBJECTIVE To explore the effects and potential mechanism of veratramine （VTM） on the proliferation of human glioblastoma U251 cells. METHODS The network pharmacology methods were adopted to screen the targets of ferroptosis related to the effects of VTM on glioblastoma， and to conduct gene ontology and Kyoto Encyclopedia of Genes and Genosomes enrichment analysis. Using U251 cells as the object， CCK-8 assay， the observation of cell morphological changes， DCFH-DA fluorescence probe method， FerroOrange fluorescence probe method and Western blot assay were used to validate the inhibitory effects of VTM on U251 cell proliferation and its possible mechanism. RESULTS Totally 462 targets of ferroptosis related to the effects of VTM on glioblastoma were screened out； they mainly enriched in biological processes such as oxidative stress and apoptosis， and cellular components such as cytoplasmic vesicles and mitochondrial membranes； they affected molecular functions such as iron ion （Fe2+） binding and DNA transcription processes， as well as iron death and phosphoinositide 3-kinase/protein kinase B signaling pathways. VTM with 40， 60， 80， 100， 120 and 140 μmol/L could significantly reduce the cell survival rate （P＜ 0.01）； VTM with 40， 80 and 120 μmol/L could cause cell atrophy and nuclear fragmentation， significantly inhibit the clone formation， increase the levels of intracellular reactive oxygen species （ROS） and Fe2+ levels， increase the expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） protein to different extents， while down-regulate the expression of glutathione peroxidase 4 （GPX4） protein （P＜0.05 or P＜0.01）. CONCLUSIONS VTM can inhibit the proliferation of U251 cells， and promote the accumulation of intracellular ROS and Fe2+， thus inducing ferroptosis； its mechanism might be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

Humans ; Brain Ischemia/therapy* ; Ischemic Stroke ; Receptors, N-Methyl-D-Aspartate ; TRPM Cation Channels

Humans ; Alzheimer Disease ; Amyloid beta-Peptides ; Neurons ; Lysosomes ; Hydrogen-Ion Concentration

This article summarizes and analyzes the reported synthetic routes of brivudine in patent and literature.2′-Deoxyuridine was employed as starting material, affording brivudine through iodization, heck coupling, hydrolysis, decarboxylation, bromination and recrystallization.After optimization of reaction conditions of each step, a synthetic route suitable for industrial production was achieved with simple synthetic process, high yield and excellent purity.

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β ₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

Objective:To investigate the expression of miRNA-34b (miR-34b) in non-small cell lung cancer (NSCLC) tissues and its effect on proliferation and invasion of human NSCLC A549 cells in vitro.Methods:The specimens of cancer tissues and paracancerous normal epithelial tissues (more than 5 cm from the edge of the tumor) were collected from 40 NSCLC patients in Shanxi Province Cancer Hospital from June 2015 to March 2017. A549 cells were transfected with miR-34b mimics (experimental group) and irrelevant sequences (negative control group), respectively. The expression of miR-34b in tissues and each group of A549 cells was detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The proliferation activity of A549 cells in the experimental group and the negative control group was detected by methyl thiazolyl tetrazolium (MTT) assay, and the invasion ability of A549 cells in the two groups was detected by Transwell assay.Results:The relative expression of miR-34b in NSCLC tissues was lower than that in paracancerous normal epithelial tissues (0.52±0.06 vs. 1.05±0.17), and the difference was statistically significant ( P < 0.001). The relative expression of miR-34b in A549 cells of the experimental group was higher than that in the negative control group, and the difference was statistically significant ( P < 0.05). MTT assay showed that the cell proliferation ability (absorbance value) of A549 cells in the experimental group was lower than that in the negative control group after cultured for 24 and 48 hours (both P < 0.01). Transwell assay showed that the number of invaded A549 cells in the experimental group was less than that in the negative control group [(49.53±5.03) cells vs. (121.00±12.06) cells, P < 0.01]. Conclusions:The expression of miR-34b is low in NSCLC tissues, and the up-regulation of miR-34b expression can inhibit the proliferation and invasion of NSCLC A549 cells.

Objective:To explore the application effect of health education based on feedback theory in perioperative nursing of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) .Methods:A total of 105 patients undergoing ERCP in the Third Hospital of Shanxi Medical University from February 2019 to June 2020 were selected as the research objects by the convenient sampling method. Patients were divided into the observation group ( n=53) and the control group ( n=52) according to random number table method. The control group was given routine health education, while the observation group was given health education based on feedback theory. The awareness of health education, self-management ability, bad mood and quality of life were compared between the two groups before and after intervention. Results:After intervention, scores of all dimensions of health education awareness questionnaire and the subscale scores of Adult Health Self-Management Ability Scale (AHSMSRS) in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . The scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) in the observation group were lower than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Health education based on feedback theory can improve the health education awareness, self-management ability of patients undergoing ERCP and improve their negative emotions.

The N-methyl-D-aspartate receptor (NMDAR) in central nerve system is mostly composed of GluN1 and GluN2 subunits. The classical NMDAR has been intensively studied. However, GluN3‑containing NMDAR is much less expressed and have atypical channel properties. Recently, accumulating evidences have revealed two types of GluN3‑containing NMDAR: glutamate-gated GluN1/GluN2/GluN3 NMDAR and glycine-gated GluN1/GluN3 NMDAR. The former may play important roles in regulating synapse maturation and pruning non-used synapses, and its elevated expression at the adult stage may alter synaptic reorganization in some neuropsychiatric disorders. The latter is expressed in the medial habenula and involves in control of aversion. This article reviews the recent progresses on the expression, functional properties of GluN3‑containing atypical NMDARs and the physiological and pathological relevance.
Central Nervous System/metabolism* ; Protein Subunits/metabolism* ; Receptors, N-Methyl-D-Aspartate ; Synapses

Objective:To investigate the association of FAT atypical cadherin 1 (FAT1) with clinicopathological parameters and prognosis in esophageal squamous cell carcinoma (ESCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 124 patients with ESCC who were admitted to Shanxi Cancer Hospital from January 2011 to December 2015 were collected. There were 85 males and 39 females, aged from 40 to 72 years, with a median age of 60 years. The ESCC tissues surgically removed and adjacent tissues specimens were collected to prepare tissue microarray for immunohistochemical staining. The 5 cases of ESCC tissues and adjacent tissues were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR). Observation indicators: (1) the expression of FAT1 protein in ESCC and adjacent tissues; (2) the expression of FAT1 RNA in ESCC and adjacent tissues; (3) the expression of FAT1 protein in ESCC tissues and its association with clinicopathological parameters; (4) follow-up and survival. Follow-up using outpatient examination and telephone interview was conducted to detect survival of patients up to February 13, 2019. The survival time was from surgical date to tumor-related death or endpoint of follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non parameter rank sum test. The Kaplan-Meier method was used to calculate survival time, and Log-rank test was used for survival analysis. Results:(1) The expression of FAT1 protein in ESCC and adjacent tissues: of 124 specimens, the 107 cases of ESCC tissues and 93 cases of adjacent tissues were finally obtained because of exfoliative tissues. There were 76 cases of ESCC tissues and corresponding adjacent tissues matched. Results of immuno-histochemical staining showed that FAT1 protein was expressed in both ESCC and adjacent tissues and was brown after staining. FAT1 was located in cytomembrane, with high expression of FAT1 as ≥75 and low expression as <75. The relative expression levels of FAT1 protein in ESCC and adjacent tissues were 68±42 and 77±37, showing a significant difference between ESCC and adjacent tissues ( t=2.380, P<0.05). (2) The expression of FAT1 RNA in ESCC and adjacent tissues: results of qRT-PCR showed that the relative expression levels of FAT1 RNA in 5 cases of ESCC and adjacent tissues were 1.6±0.4 and 2.5±0.3, with a significant difference between them ( t=3.560, P<0.05). (3) The expression of FAT1 protein in ESCC tissues and its association with clinicopathological parameters: of the 107 ESCC patients, 58 cases had high expression of FAT1. There were 42 and 16 cases with high expression of FAT1 in 65 non-drinking patients and 42 drinking patients, respectively, showing a significant difference between them ( χ2=7.229, P<0.05). (4) Follow-up and survival: 96 of 107 ESCC patients were followed up for 38.0?94.9 months, with a median follow-up time of 45.9 months. Survival analysis showed that the survival time of patients with high FAT1 expression was 24 months, versus 22 months of patients with low FAT1 expression, indicating no significant difference between them ( χ2=1.773, P>0.05). Results of subgroup analysis showed that the survival time was 24 months and 21 months of female patients with high and low FAT1 expression, 23 months and 22 months of non-smoking patients with high FAT1 expression and low FAT1 expression, 23 months and 21 months of non-drinking patients with high FAT1 expression and low FAT1 expression, respectively, showing significant differences between them ( χ2=8.769, 12.827, 10.724, P<0.05). Conclusions:The expression of FAT1 in ESCC tissues is low. Female, non-smoking and non-drinking ESCC patients with high FAT1 expression have good survival.

Background: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea and an important cause of death in hospitalized patients with diarrhea. However, there are not sufficient clinical researches on the risk factors of CDI. Aims: To investigate the risk factors of CDI in hospitalized patients with diarrhea. Methods: A total of 230 hospitalized diarrhea patients who received Clostridium difficile test from January 2015 to January 2019 at the Second Hospital of Hebei Medical University were collected. The patients were divided into CDI group and non-CDI group. Logistic regression analysis was performed to investigate the risk factors of CDI. Results: Compared with non-CDI group, patients in CDI group had a longer hospital stay (P<0.05) and a higher proportion of surgery in the past 6 months (P<0.05). The number of comorbidities in CDI group was higher than that in non-CDI group (P<0.05), and the ratio of gastrointestinal disease, cardiovascular disease, blood/immune system disease, nervous system disease in CDI group were higher than those in non-CDI group (P<0.05). Multivariate analysis showed the number of comorbidities (OR=3.215, 95% CI: 1.576-4.743; P=0.003), gastrointestinal disease (OR=4.135, 95% CI: 3.048-11.416; P=0.000), surgical history (OR=6.734, 95% CI: 2.692-15.849; P=0.000) and antibiotic use (OR=5.996, 95% CI: 2.173-15.481; P=0.000) were risk factors of CDI, especially the use of quinolone antibiotics (OR=4.769, 95% CI: 2.138-14.757; P=0.000). Conclusions: CDI can prolong the hospital stay of patients with diarrhea. Number of comorbidities, underlying gastrointestinal disease, recent history of surgery and antibiotic use, especially the use of quinolone antibiotics are risk factors of CDI in hospitalized patients with diarrhea.