[Current status of thromboembolism risk assessment in patients hospitalized with non-valvular atrial fibrillation in tertiary hospitals in China].

Objective: To analyze the current status, trend and predictors of thromboembolism risk assessment in patients hospitalized with non-valvular atrial fibrillation (NVAF) in tertiary hospitals in China. Methods: The study was based on data from the Improving Care for Cardiovascular disease in China (CCC)-Atrial Fibrillation (AF) project. About 10% of the tertiary hospitals in each geographic-economic stratum were recruited. Participating hospitals reported the first 10 to 20 patients with a discharge diagnosis of atrial fibrillation monthly. From February 2015 to December 2019, a total of 49 104 NVAF patients from 151 tertiary hospitals in 30 provinces, municipalities and autonomous regions were enrolled. Clinical data of the patients was collected. The proportion of NVAF patients receiving thromboembolism risk assessment, variations in the proportion between different hospitals, the time trend of the application of thromboembolism risk assessment, and the predictors of the application of thromboembolism risk assessment were analyzed. Results: The age of the NVAF patients was (68.7±12.1) years, 27 709 patients (56.4%) were male. Only 17 251 patients (35.1%) received thromboembolism risk assessment. The proportion varied substantially between hospitals with the lowest value of 0 and the highest value of 100%. Among the hospitals, which enrolled more than 30 patients, no patients received thromboembolism risk assessment in 18.4% (26/141) of the hospitals, more than 50% of the patients received thromboembolism risk assessment in 21.3% (30/141) of the hospitals, and all the patients received thromboembolism risk assessment in only 1 hospital. The proportion of NVAF patients receiving thromboembolism risk assessment was 16.2% (220/1 362) in the first quarter of 2015, and significantly increased to 67.1% (1 054/1 572) in the last quarter of 2019 (P<0.001). Patients' characteristics were associated with the application of thromboembolism risk assessment. The odds of receiving thromboembolism risk assessment was lower in male patients compared to female patients(OR=0.94,95%CI 0.89-0.99), lower in patients with acute coronary syndrome or other cardiovascular diseases compared to those with AF as the primary admission reason (OR=0.59, 95%CI 0.55-0.63, OR=0.52, 95%CI 0.45-0.61, respectively), and lower in patients with paroxysmal, persistent and long-standing/permanent AF compared to those with first detected AF (OR=0.62, 95%CI 0.57-0.67, OR=0.72, 95%CI 0.66-0.79, OR=0.57, 95%CI 0.52-0.64, respectively). The odds was higher in patients with a history of hypertension, heart failure, stroke/TIA, and previous anticoagulant therapy compared to those without the above conditions (OR=1.17, 95%CI 1.11-1.23, OR=1.18, 95%CI 1.07-1.30, OR=1.17, 95%CI 1.08-1.27, OR=1.28, 95%CI 1.19-1.37, respectively) (P all<0.05). Conclusion: Thromboembolism risk assessment was underused in patients hospitalized with NVAF in tertiary hospitals in China, and there were substantial variations between hospitals in the application of thromboembolism risk assessment. The application of thromboembolism risk assessment in tertiary hospitals has been improved in recent years, but there is still plenty of room for future improvement. Patients' characteristics could affect the application of thromboembolism risk assessment in China.

[Clinical effects of dorsal perforator fascia pedicle flap of the deep palmar arch in the repair of skin and soft tissue defects of finger web area].

Objective: To explore the clinical effects of dorsal perforator fascia pedicle flap of the deep palmar arch in the repair of skin and soft tissue defects of finger web area. Methods: Eleven patients (7 males and 4 females, aged from 18 to 73 years) with soft tissue defects of finger web area in distal dorsal side were admitted to Xinhua Hospital (Chongming) of Shanghai Jiao Tong University School of Medicine from October 2010 to September 2018. The sizes of skin and soft tissue defects ranged from 2.5 cm×1.5 cm to 6.0 cm×2.5 cm. According to the origin, course, branches, and distribution of the dorsal perforator of deep palmar arch, and the anatomical characteristics with vascular network of dorsal carpal and dorsal metacarpal, dorsal perforator fascia pedicle flaps of the deep palmar arch from the back of the injured hands were designed and transferred to repair the wounds of finger web area in distal dorsal side. The sizes of the flaps of patients ranged from 3.5 cm×2.0 cm to 6.5 cm×3.0 cm. The donor sites were sutured directly or covered with free forearm full-thickness skin graft. The clinical effects and swelling degree of flaps in early and late stages were evaluated during the follow-up of 3 to 36 months post surgery. Results: All the flaps survived in 11 patients, the incisions in donor and recipient sites were healed. During the follow-up of 3 to 36 months post surgery, the survival of flaps was good, and the appearance, color, and elasticity were close to normal skin, with two-point discrimination distance of 7 to 10 mm and sensory function recovery of grade S(3). The wounds in donor site had small scar without infection. The efficacy was evaluated as satisfactory in 8 patients, general in 3 patients, and dissatisfactory in no patient. Flap swelling rating in early stage was 1st degree in 7 patients, 2nd degree in 2 patients, and 3rd degree in 2 patients. Flap swelling rating in late stage was 1st degree in 8 patients, 2nd degree in 2 patients, and 3rd degree in 1 patient. The extension and flexion of the metacarpal and interphalangeal joints were basically normal and the patients were satisfied with the outcomes. Conclusions: Based on the dorsal perforator of deep palmar arch, dorsal perforator fascia pedicle flap of the deep palmar arch is reliable to transfer to repair skin and soft tissue defects of finger web area in distal dorsal side, which is worthy of promotion in clinic.

MiR-15b ameliorates SONFH by targeting Smad7 and inhibiting osteogenic differentiation of BMSCs.

OBJECTIVE: The aim of this study was to explore the role of micro ribonucleic acid (miR)-15b in steroid-induced osteonecrosis of the femoral head (SONFH) and its potential mechanism. PATIENTS AND METHODS: Bone marrow tissues were collected from 5 patients with glucocorticoid (GC)-induced ONFH (GC-ONFH, GC group) and 5 patients with secondary ONFH (control group) undergoing total hip replacement in our hospital from July 2016 to August 2017. Subsequently, bone marrow mesenchymal stem cells (BMSCs) were separated from bone marrow extracted and cultured in vitro. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) assay was used to detect differentially expressed miRNAs in BMSCs of patients in GC group and control group. BMSCs were treated with different concentrations of GC. Next, the effect of GC on tmiR-15b expression level was detected via qRT-PCR. Alizarin red staining assay was performed to evaluate the effect of miR-15b on osteogenic differentiation of BMSCs. Meanwhile, the potential targets of miR-15b were predicted using bioinformatics software and validated through luciferase reporter gene assay, respectively. Additionally, Western blotting was conducted to determine the effect of miR-15b on the protein expression of the transforming growth factor beta (TGF-ß) signaling pathway. RESULTS: Flow cytometry demonstrated that the proportion of cluster of differentiation 44 (CD44)-positive cells was 99.7%, while that of CD45-positive cells was only 0.17% in cultured BMSCs. This suggested that the purity of BMSCs was relatively high. QRT-PCR assay indicated that the expression level of miR-15b declined significantly in BMSCs of GC group when compared with control group (p<0.01). The osteogenic differentiation capacity of BMSCs was significantly strengthened in GC group compared with control group (p<0.01). Subsequent qRT-PCR assay revealed that GC down-regulated the expression level of miR-15b in a dose-dependent manner. Besides, the osteogenic differentiation capacity of cells was remarkably strengthened in miR-15b mimic treatment group when compared with control group (p<0.01). Bioinformatics software (TargetScan) predicted that drosophila mothers against decapentaplegic protein 7 (Smad7) might be a potential target of miR-15b, which was indicated by luciferase reporter gene assay. In comparison with control group, miR-15b mimic treatment group exhibited significantly down-regulated protein expression level of Smad7, increased expression level of phosphorylated (p)-Smad2/3 and up-regulated messenger RNA (mRNA) expression level of runt-related transcription factor 2 (Runx2). However, the protein expression level of Smad7 and p-Smad2/3 and the mRNA expression level of Runx2 exhibited opposite trends in miR-15b inhibitor treatment group. CONCLUSIONS: MiR-15b relieves SONFH by targeting Smad7 and repressing osteogenic differentiation of BMSCs.

Bi-level evolutionary graphs with multi-fitness.

Evolutionary graphs (EGs) were initially introduced in 2005 and give an outlet for the evolutionary dynamic determined by the population structures, the fitness of the mutants and the number of the individuals. Bi-level EGs with different fitness are discussed. The corresponding fixation probability is given, especially when the lower level and the upper level are all isothermal. The optimisation fixation probabilities are also built if the lower and the upper graphs are all isothermal structures and the number of the total individuals is finite. At last, some applications to the system biology are involved.

Dexamethasone inhibits insulin binding to insulin-degrading enzyme and cytosolic insulin-binding protein p82.

We recently demonstrated that insulin specifically binds to several cytosolic insulin-binding proteins (CIBPs) including insulin-degrading enzyme (IDE) and CIBP p82 in cytosol isolated from H35 rat hepatoma cells. Insulin binding to these CIBPs was regulated by culture conditions, such as serum or insulin. In the present study, we examined the effect of dexamethasone on insulin binding to CIBPs in H35 cells. When the cells were treated with 100 nM dexamethasone for 24 hrs, insulin binding to IDE and CIBP p82 was decreased by about 50% without decreasing the expression level of IDE. Insulin added with the dexamethasone prevented the steroid's effect. Furthermore, dexamethasone directly blocked insulin binding to CIBPs in isolated cytosol. These results suggest that dexamethasone, directly or as a complex with other proteins, binds to IDE and CIBP p82 and changes their ability to bind insulin, possibly by inducing a conformational change or by blocking insulin binding sites. IDE was recently identified as a receptor accessory factor for androgen and glucocorticoid receptors and plays an important role in the regulation of gene transcriptional responses. Combined with previous reports, our findings suggest IDE and other CIBPs such as CIBP p82 may play a role in the cross-talk between insulin and the signal transduction pathways of steroid hormones.

Insulin-induced egr-1 expression in Chinese hamster ovary cells is insulin receptor and insulin receptor substrate-1 phosphorylation-independent. Evidence of an alternative signal transduction pathway.

Insulin's effects primarily are initiated by insulin binding to its plasma membrane receptor and the sequential tyrosine phosphorylation of the insulin receptor and intracellular substrates, such as insulin receptor substrate-1 (IRS-1). However, studies suggest some insulin effects, including those at the nucleus, may not be regulated by this pathway. The present study compared the levels of insulin binding, insulin receptor and IRS-1 tyrosine phosphorylation, and phosphatidylinositol 3'-kinase activity to immediate early gene c-fos and egr-1 mRNA expression in Chinese hamster ovary (CHO) cells expressing only neomycin-resistant plasmid (CHONEO), overexpressing wild type human insulin receptor (CHOHIRc) or ATP binding site-mutated insulin receptors (CHOA1018K). Insulin binding in CHONEO cells was markedly lower than that in other cell types. 10 nM insulin significantly increased tyrosine phosphorylation of insulin receptor and IRS-1 in CHOHIRc cells. Phosphorylation of insulin receptor and IRS-1 in CHONEO and CHOA1018K cells was not detected in the presence or absence of insulin. Similarly, insulin increased phosphatidylinositol 3-kinase activity only in CHOHIRc cells. As determined by Northern blot, nuclear run-on analysis, and in situ hybridization, insulin induced c-fos mRNA expression, through transcription, in CHOHIRc cells but not in CHONEO and CHOA1018K cells, consistent with previous reports. In contrast, all three cell types showed a similar insulin dose-dependent increase of egr-1 mRNA expression through transcription. These data indicated that insulin-induced egr-1 mRNA expression did not correlate with the levels of insulin binding to insulin receptor or phosphorylation of insulin receptor and IRS-1. These results suggest that different mechanisms are involved in induction of c-fos and egr-1 mRNA expression by insulin, the former by the more classic insulin receptor tyrosine kinase pathway and the latter by a yet to be determined alternative signal transduction pathway.