Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

In the all-media era, communication channels are increasingly diversified and the modes of communication are undergoing profound changes. Same medical institutions ignore the development of all media, which lead to rigid and backward communication situation, affect the healthy development of medical and health undertakings. Mastering and making good use of the advantages and characteristics of communication in the all-media era will also provide more motivation and possibilities for strengthening ideological work. This paper expounded the significance of strengthening the dissemination of socialist ideology in hospitals, proposed the opportunities and challenges faced by hospitals in strengthening the dissemination of socialist ideology in the all-media era, and then put forward specific coping strategies combined with the actual situation of hospitals.

AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC

Background and Objectives: miR-450a-5p was involved in fat formation, however, its role in insulin resistance remains unclear. This study investigated the effects of miR-450a-5p on endothelial cells, with the aim of finding a potential target for diabetes mellitus. Methods: and Results: Human umbilical vein endothelial cells (HUVECs) were treated with low-glucose, high-glucose, methylglyoxal (MGO), and insulin alone or in combination with MGO. The expression of miR-450a-5p in treated cells was measured by quantitative real-time polymerase chain reaction (qRT-PCR) assays. The cell activity, migration and fat formation were determined by MTT experiments, Transwell assay and oil red O staining. The expressions of eNOS/ AKT pathway-related proteins in cells were assessed by Western blot (WB) analysis. Furthermore, the target gene of miR-450a-5p was analyzed by double-luciferase reporter analysis, and its effects on eNOS/AKT pathway were estimated. We found that the expression of miR-450a-5p was decreased obviously in endothelial cells treated with high-glucose and MGO. In vitro cell experiments showed that MGO could not only promote the activity of endothelial cells, but also accelerate cell migration and fat accumulation, which, however, could be reversed by up-regulation of miR-450a-5p. Moreover, MGO inhibited eNOS/AKT pathway activation and NO release mediated by insulin, and such effects were reversed by up-regulation of miR-450a-5p. Furthermore, CREB was the target gene for miR-450a-5p, had an activation effect on the eNOS/AKT pathway. Conclusions Up-regulated miR-450a-5p eliminates MGO-induced insulin resistance via targeting CREB, and therefore could be used as a potential target to improve insulin resistance and treat patients with diabetes-related diseases.

Objective To evaluate the efficacy,bleeding profile and safety of low-dose levonorgestrel-releasing intrauterine system (LNG-IUS 8) in Chinese healthy women of childbearing age.Methods A multi-center,open-label,single-arm clinical trial conducted at 16 centres in China enrolled 773 healthy women of childbearing age (mean age 31.6 years old,range 18 to 40 years old),who demanded contraception,from April 2006 to June 2013.All women placed LNG-IUS 8 for 3 years and then been followed up at 3,6,9,12,18,24,30,36 months.The efficacy variables including pregnancy rate and expulsion rate were analyzed using life table,while observing adverse events (AE) to evaluate the safety.The bleeding profile happened during the study was assessed using 90-day reference intervals (World Health Organization criteria).Results Eight pregnancies occurred among 773 women,resulting in a overall Pearl index of 0.42 per 100 women years.The 3-year cumulative pregnancy rate was 0.37 per 100 women years and the 3-year cumulative expulsion rate was 1.99 per 100 women years.The number of women with bleeding/spotting reduced and the bleeding/spotting days declined over time.Totally 219 AE were reported related to LNG-IUS 8 placements.The most common AE were vaginal bleeding (8.2％,63/773)and the ovarian cyst (6.2％,52/773).LNG-IUS 8 had an improving effect on dysmenorrhea that the percentage of women with dysmenorrhea as well as the days of dysmenorrhea decreased over time.The percentage of women satisfied or very satisfied with LNG-IUS 8 was 87.2％ (622/713).Conclusion LNG-IUS 8 is highly effective and safe for Chinese healthy women of childbearing age.

Objective To analyze the causes of hypoglycemia coma in emergency diabetes patients and its corresponding nursing strategies.Methods The reasons of hypoglycemia coma was retrospectively analyzed in our hospital and the risk factors of hypoglycemic coma were analyzed by multivariate logistic regression,and the corresponding nursing strategies were summarized.Results Of the 767 critically ill patients,100 (13.04％) had hypoglycemia,among whom 27 patients (3.52％) had severe hypoglycemia.Multivariate logistic regression analysis showed that patients with type 2 diabetes history,hypoglycemic drugs therapy,hypoproteinemia,renal insufficiency,hemodialysis,malnutrition were risk factors for hypoglycemic coma.While normal hemoglobin was a protective factor for hypoglycemic coma.Conclusion Hypoglycemia is the result of multiple factors in emergency patients.Reasonable nursing measures can effectively prevent the occurrence of hypoglycemic coma in emergency patients.

Objective To analyze the causes of hypoglycemia coma in emergency diabetes patients and its corresponding nursing strategies.Methods The reasons of hypoglycemia coma was retrospectively analyzed in our hospital and the risk factors of hypoglycemic coma were analyzed by multivariate logistic regression,and the corresponding nursing strategies were summarized.Results Of the 767 critically ill patients,100 (13.04％) had hypoglycemia,among whom 27 patients (3.52％) had severe hypoglycemia.Multivariate logistic regression analysis showed that patients with type 2 diabetes history,hypoglycemic drugs therapy,hypoproteinemia,renal insufficiency,hemodialysis,malnutrition were risk factors for hypoglycemic coma.While normal hemoglobin was a protective factor for hypoglycemic coma.Conclusion Hypoglycemia is the result of multiple factors in emergency patients.Reasonable nursing measures can effectively prevent the occurrence of hypoglycemic coma in emergency patients.

Objective To study the correlation between individual gene polymorphisms of transforming growth factor (TGF)-β1 + 869 T/C,tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) + 1525 G/A genes and nodular thyroid disease.Methods From September 2007 to December 2009,a total of 544 patients with nodular thyroid disease diagnosed in the Department of Endocrinology,The First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology were selected,including 136 cases of nodular goiter patients (node group),132 cases of thyroid tumor (adenoma group),146 cases of Graves patients (GD group),and 130 cases of Hashimoto's thyroiditis (HT group).One hundred and thirty-five healthy subjects were enrolled as control group.Two milliliters of fasting venous blood of all subjects were collected.Polymorphisms of the TGF-β1 + 869 T/C and the TRAIL 1525 A/G genes were identified by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and the restriction fragment length polymorphism (PCR-RFLP) methods.Results TGF-β1 + 869 T/C:The CC genotypes and C allele frequencies of nodular goiter group [47.0％(64/136),63.2％(172/ 272)] were significantly higher than those of normal control group [18.0％(22/135),45.2％ (122/270); x2 =30.76,17.79,all P ＜ 0.05].The genotypes and allele frequencies of adenoma group[42.4％ (56/132),59.1％ (156/264)] were significantly higher than those of the normal control group (x2 =24.40,10.34,all P ＜ 0.05).The risk of population carrying the C allele suffering from nodular goiter was 2.086 times of those carrying the T allele (OR =2.086; 95％ CI:1.480-2.943).The risk of population carrying the C allele suffering from adenoma was 1.752 times of those carrying the T allele (OR =1.752,95％ CI:1.244-2.469).TRAIL + 1525 G/A:the genotypes and allele frequencies of nodular goiter group [40.4％ (55/136),62.9％ (171/272)] were significantly higher than those of normal control group [12.0％ (16/135),48.5％ (131/270); x2 =9.176,11.307,all P ＜ 0.05].The genotypes and allele frequencies of adenoma group[53.3％ (70/132),73.1％ (193/264)] were significantly higher than those of the normal control group (x2 =9.806,33.82,all P ＜ 0.05).The risk of population carrying the G allele suffering from nodular goiter was 1.796 times of those carrying the A allele (OR =1.796,95％ CI:1.275-2.531).The risk of population carrying the G allele suffering from adenoma was 2.884 times of those carrying the A allele (OR =2.884,95％ CI:2.009-4.142).Conclusions TGF-β1 + 869 T/C and TRAIL + 1525 G/A gene polymorphisms may be related to the incidence of nodular thyroid diseases; G allele of TRAIL and C allele of TGF-β1 may be predisposing genes of patients with nodular goiter.

Nanopore-based sequencers, as the fourth-generation DNA sequencing technology, have the potential to quickly and reliably sequence the entire human genome for less than $1000, and possibly for even less than$100. The single-molecule techniques used by this technology allow us to further study the interaction between DNA and protein, as well as between protein and protein. Nanopore analysis opens a new door to molecular biology investigation at the single-molecule scale. In this article, we have reviewed academic achievements in nanopore technology from the past as well as the latest advances, including both biological and solid-state nanopores, and discussed their recent and potential applications.