Construction of an index system of core competence assessment for sleep medicine nurse specialists in China: a Delphi study.

AIM: To construct an evaluation index system for the core competence of nurses in sleep medicine specialties. BACKGROUND: Specialized nurses in sleep medicine must handle treatment, nursing, and management well, which requires nurses to have excellent competence in knowledge, skills, and ability. However, a competency evaluation system for sleep medicine nurses has not been established in China. METHODS: We used a literature review and an expert meeting to establish a draft indicator system. Subsequently, two rounds of correspondence were conducted with 27 experts from 5 provinces using the Delphi method to solicit their opinions on the core competency evaluation indicators for sleep medicine nurse specialists and to qualitatively evaluate the experts' scores. The consensus was defined in advance as a mean score of 4.0 or above, with at least 75% agreement among participants. In this way, the final indicator framework was determined. RESULTS: The final evaluation indexes of the core competencies for sleep medicine Nurse Specialists included 6 first-level indexes (Practical ability, Theoretical Knowledge, Critical thinking, Communication and coordination, Nursing Management, and Professional Development), 16 s-level indexes, and 64 third-level indexes. The effective response rates of the two expert consultation rounds were 100%. The expert authority coefficients were 0.878 and 0.865 in the first and second rounds of consultation, respectively. In the second round of consultation, the first, second, and third indexes of Kendall's coefficient of concordance were 0.373, 0.351, and 0.286, respectively (P < 0.05). CONCLUSION: The core competence evaluation index system for sleep medicine nurses established in this study is scientific and reliable and can provide a theoretical reference for the training, assessment, and evaluation of sleep medicine nurses in the future. IMPLICATIONS FOR NURSING MANAGEMENT: The evaluation index system of sleep medicine nurses' core competence will provide an effective practical framework for nursing management to evaluate, train, and examine the core competence of sleep medicine nurses.

DCBLD2 deletion increases hyperglycemia and induces vascular remodeling by inhibiting insulin receptor recycling in endothelial cells.

Discoidin, CUB, LCCL domain-containing 2 (DCBLD2) is a type I transmembrane protein with a similar structure to neuropilin, which acts as a co-receptor for certain receptor tyrosine kinases (RTKs). The insulin receptor is an RTK and plays a critical role in endothelial cell function and glycolysis. However, how and whether DCBLD2 regulates insulin receptor activity in endothelial cells is poorly understood. Diabetes was induced through treatment of Dcbld2 global-genome knockout mice and endothelium-specific knockout mice with streptozotocin. Vascular ultrasound, vascular tension test, and hematoxylin and eosin staining were performed to assess endothelial function and aortic remodeling. Glycolytic rate assays, real-time PCR and western blotting were used to investigate the effects of DCBLD2 on glycolytic activity and insulin receptor (InsR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in endothelial cells. Co-immunoprecipitation was used to assess the effects of DCBLD2 on insulin receptor endocytosis and recycling. Membrane and cytoplasmic proteins were isolated to determine whether DCBLD2 could affect the localization of the insulin receptor. We found that Dcbld2 deletion exacerbated endothelial dysfunction and vascular remodeling in diabetic mice. Both Dcbld2 knockdown and Dcbld2 deletion inhibited glycolysis and the InsR/PI3K/Akt signaling pathway in endothelial cells. Furthermore, Dcbld2 deletion inhibited insulin receptor recycling. Taken together, Dcbld2 deficiency exacerbated diabetic endothelial dysfunction and vascular remodeling by inhibiting the InsR/PI3K/Akt pathway in endothelial cells through the inhibition of Rab11-dependent insulin receptor recycling. Our data suggest that DCBLD2 is a potential therapeutic target for diabetes and cardiovascular diseases.

DCBLD2 regulates vascular hyperplasia by modulating the platelet derived growth factor receptor-ß endocytosis through Caveolin-1 in vascular smooth muscle cells.

DCBLD2 is a neuropilin-like transmembrane protein that is up-regulated during arterial remodeling in humans, rats, and mice. Activation of PDGFR-ß via PDGF triggers receptor phosphorylation and endocytosis. Subsequent activation of downstream signals leads to the stimulation of phenotypic conversion of VSMCs and arterial wall proliferation, which are common pathological changes in vascular remodeling diseases such as atherosclerosis, hypertension, and restenosis after angioplasty. In this study, we hypothesized that DCBLD2 regulates neointimal hyperplasia through the regulation of PDGFR-ß endocytosis of vascular smooth muscle cells (VSMCs) through Caveolin-1 (Cav-1). Compared with wild-type (WT) mice or control littermate mice, the germline or VSMC conditional deletion of the Dcbld2 gene resulted in a significant increase in the thickness of the tunica media in the carotid artery ligation. To elucidate the underlying molecular mechanisms, VSMCs were isolated from the aorta of WT or Dcbld2-/- mice and were stimulated with PDGF. Western blotting assays demonstrated that Dcbld2 deletion increased the PDGF signaling pathway. Biotin labeling test and membrane-cytosol separation test showed that after DCBLD2 was knocked down or knocked out, the level of PDGFR-ß on the cell membrane was significantly reduced, while the amount of PDGFR-ß in the cytoplasm increased. Co-immunoprecipitation experiments showed that after DCBLD2 gene knock-out, the binding of PDGFR-ß and Cav-1 in the cytoplasm significantly increased. Double immunofluorescence staining showed that PDGFR-ß accumulated Cav-1/lysosomes earlier than for control cells, which indicated that DCBLD2 gene knock-down or deletion accelerated the endocytosis of PDGF-induced PDGFR-ß in VSMCs. In order to confirm that DCBLD2 affects the relationship between Cav-1 and PDGFR-ß, proteins extracted from VSMCs cultured in vitro were derived from WT and Dcbld2-/- mice, whereas co-immunoprecipitation suggested that the combination of DCBLD2 and Cav-1 reduced the bond between Cav-1 and PDGFR-ß, and DCBLD2 knock-out was able to enhance the interaction between Cav-1 and PDGFR-ß. Therefore, the current results suggest that DCBLD2 may inhibit the caveolae-dependent endocytosis of PDGFR-ß by anchoring the receptor on the cell membrane. Based on its ability to regulate the activity of PDGFR-ß, DCBLD2 may be a novel therapeutic target for the treatment of cardiovascular diseases.

Developmental Stage-Specific Embryonic Induction of HepG2 Cell Differentiation.

BACKGROUND: Although hepatocellular carcinoma cells can sometimes undergo differentiation in an embryonic microenvironment, the mechanism is poorly understood. AIM: The developmental stage-specific embryonic induction of tumor cell differentiation was investigated. METHODS: Both chick and mouse liver extracts and hepatoblast-enriched cells at different developmental stages were used to treat human hepatoma HepG2 cells, and the effects on the induction of differentiation were evaluated. The nuclear factors controlling differentiation, hepatocyte nuclear factor (HNF)-4α, HNF-1α, HNF-6 and upstream stimulatory factor-1 (USF-1), and the oncogene Myc and alpha-fetoprotein (AFP) were measured. HNF-4α RNA interference was used to verify the role of HNF-4α. Embryonic induction effects were further tested in vivo by injecting HepG2 tumor cells into immunodeficient nude mice. RESULTS: The 9-11-days chick liver extracts and 13.5-14.5-days mouse hepatoblast-enriched cells could inhibit proliferation and induce differentiation of HepG2 cells, leading to either death or maturation to hepatocytes. The maturation of surviving HepG2 cells was confirmed by increases in the expressions of HNF-4α, HNF-1α, HNF-6, and USF-1, and decreases in Myc and AFP. The embryonic induction of HepG2 cell maturation could be attenuated by HNF-4α RNA interference. Furthermore, the 13.5-days mouse hepatoblast culture completely eliminated HepG2 tumors with inhibited Myc and induced HNF-4α, confirming this embryonic induction effect in vivo. CONCLUSIONS: This study demonstrated that developmental stage-specific embryonic induction of HepG2 cell differentiation might help in understanding embryonic differentiation and oncogenesis.

Developmental Stage-Specific Hepatocytes Induce Maturation of HepG2 Cells by Rebuilding the Regulatory Circuit.

On the basis of their characteristics, we presume that developmental stage-specific hepatocytes should have the ability to induce maturation of hepatoma cells. A regulatory circuit formed by hepatocyte nuclear factor (HNF)-4α, HNF-1α, HNF-6 and the upstream stimulatory factor (USF-1) play a key role in the maturation of embryonic hepatocytes; however, it is unclear whether the regulatory circuit mediates the embryonic induction of hepatoma cell maturation. In this study, 12.5-d to 15.5-d mouse embryonic hepatocytes or their medium were used to coculture or treat HepG2 cells, and the induced maturation was evaluated in vitro and in vivo. In the induced HepG2 cells, the components of the regulatory circuit were detected, their cross-regulation was evaluated and HNF-4α RNA interference was performed. We found that 13.5-d to 14.5-d embryonic hepatocytes could induce HepG2 cell maturation, demonstrated by morphological changes, increased maturation markers and decreased c-Myc and α-fetoprotein (AFP) in vitro. The majority of HepG2 tumors were eliminated by 13.5-d embryonic induction in vivo. All components of the regulatory circuit were upregulated and the binding of HNF-4α, HNF-1α, HNF-6 and USF-1 to their target sites was promoted to rebuild the regulatory circuit in the induced HepG2 cells. Moreover, RNA interference targeting HNF-4α, which is the core of the regulatory circuit, attenuated the induced maturation of HepG2 cells with downregulation of the regulatory circuit. These results revealed that developmental stage-specific hepatocytes could induce the maturation of HepG2 cells by rebuilding the regulatory circuit.

Prebiotics and oxidative stress in constipated rats.

OBJECTIVES: Constipation can adversely affect children's health, with disorders of host immunity and enhanced oxidative stress. As nondigestible carbohydrates, prebiotics can affect the host with constipation; however, whether the prebiotics have effects on the content of intestinal secretory immunoglobulin A (sIgA) and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in constipation has not been fully clarified. METHODS: In the present study, constipation was induced in female Sprague-Dawley rats by diphenoxylate, and the prebiotics dissolved in milk were used as an intervention. The indicators of intestinal peristalsis, including the time of passing black stool initially, the grains of black stool in 24 hours, and the advance rate of ponceau, were measured. The content of intestinal sIgA was detected by enzyme-linked immunosorbent assay. The contents of SOD and MDA in serum and intestinal tissue were analyzed by their detection kits. RESULTS: The changes in intestinal peristalsis show obvious constipation. The content of intestinal sIgA decreases, the content of SOD decreases, but the content of MDA increases in constipated rats. Prebiotics can attenuate the constipation-caused abnormal indicators significantly. CONCLUSIONS: Prebiotics can attenuate decreased intestinal immunity and enhanced oxidative stress, in addition to reduced intestinal peristalsis and of the constipated rats.