The key words, social network and author cooperation network in papers ( published in 2003-2014 ) on reform in domestic public hospitals were analyzed using Ucinet and CiteSpace visual softwares with CNKI as the data source.The current situation in reform in domestic public hospitals was revealed by mining its research hotspots, progress and author cooperation .Some suggestions were put forward for strengthening the reform in domestic public hospitals .

Objective:To investigate the relationship between serum vascular endothelial growth factor (VEGF), peripheral blood microRNA-126 (miR-126) and the number and distribution of cerebral microbleeds (CMBs).Methods:Consecutive patients with non-acute ischemic cerebrovascular disease admitted to the Department of Neurology, the First Affiliated Hospital of Baotou Medical College from June 2019 to June 2020 were enrolled. The clinical data were collected, 3.0 T MRI examination was performed, and susceptibility-weighted imaging was used to detect CMBs. The serum VEGF concentration was detected by enzyme-linked immunosorbent assay, and miR-126 was detected by fluorescence quantitative polymerase chain reaction. Multivariate logistic regression analysis was used to determine the independent influencing factors of CMBs. Multiple linear regression analysis was used to determine the correlation between serum VEGF concentration, miR-126 in peripheral blood and the number of CBMs. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum VEGF concentration and relative expression of miR-126 in peripheral blood for CMBs. Results:A total of 193 patients with non-acute ischemic cerebrovascular disease were enrolled, including 110 patients (57.0%) in the non-CMBs group, 20 (10.4%) in the strictly lobar CMBs group and 63 patients (32.6%) in non-strictly lobar CMBs group. The comparison among the three groups showed that age might be a risk factor for strictly lobar CMBs, while higher VEGF, higher cystatin C level, lower relative expression of miR-126 in peripheral blood, hypertension and previous stroke or transient ischemic attack might be the risk factors for non-strictly lobar CMBs. Multivariate logistic regression analysis showed that higher serum VEGF concentration was an independent risk factor for non-strictly lobar CMBs (odds ratio 1.186, 95% confidence interval 1.035-1.358; P=0.014), while the higher relative expression of miR-126 was an independent protective factor for non-strictly lobar CMBs (odds ratio 0.154, 95% confidence interval 0-0.269; P=0.026). Multiple linear regression analysis showed that higher serum VEGF concentration ( r=0.848, P<0.001) and the lower relative expression of miR-126 ( r=-0.043, P=0.035) significantly increased the number of CMBs. ROC curve analysis showed that the area under the curve of serum VEGF for predicting non-strictly lobar CMBs was 0.803 (95% confidence interval 0.741-0.865), the optimal cut-off value was 120.55 ng/L, the sensitivity was 70.7%, and the specificity was 75.5%. Conclusions:In patients with non-acute ischemic cerebrovascular disease, there is a significant correlation between serum VEGF concentration and the relative expression of miR-126 in peripheral blood and the number and distribution of CMBs. Serum VEGF can be used as a biomarker for predicting the presence of non-strictly lobar CMBs.

Aim To observate the effect of chemokine receptor(CXCR4) gene transfection on biological behavior of bone marrow mesenchymal stem cells in vitro.Methods Firstly, bone marrow mesenchymal stem cells were divided into three groups:GFP(transfected GFP into MSCs), CXCR4+(transfected CXCR4+ into MSCs) and CXCR4-(transfected CXCR4-into MSCs) group.Then, their capacity of proliferation, differentiation and migration ability (in vitro) was assessed with immunofluorescence cytochemistry method, flow cytometry assay and Transwell cell chemotaxis test.Results The high or low expression of CXCR4 had no effect on their ability of proliferation and differentiation into lung tissue.Compared with GFP group, however, CXCR4+-MSCs group significantly increased the number of migrating cells, while CXCR4——MSCs group showed no change in the number of migrating cells.Conclusions The proliferation and differentiation capacities are not affected by the high or low expression of CXCR4.The high expression of CXCR4 can significantly enhance the migration ability of MSCs to inflammatory lesions, and the low one has no effect on the migration of the cells.After the transplantation of MSCs, CXCR4′s high expression will access to the lesion area to participate in tissue repairing rapidly and largely, significantly enhancing the therapeutic efficacy.

OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis (UC), a recurrent and intractable inflammatory bowel disease. METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis, HLJ2 decreased weight loss, colon contracture, disease activity index (DAI), colon mucosa damage index (CMDI) and histopathological index (HI). HLJ2 also decreased myelo?peroxidase(MPO) activity and reduced production of the inflammatory cytokines TNF- α, IL- 1β, andIL- 6. HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate (DSS) and increased the expression of ZO-1 and claudin-1. Fecal 16s rRNA high-throughput sequencing demon?strated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2, including increased abundance of probiotics such as Lachnospiraceae, Prevotellaceae, and Lactobacillaceae. At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microor?ganisms such as Bacteroidaceae, Porphyromonadaceae, Deferribacteraceae, and Pseudomonadaceae in HLJ2- treated mice compared with untreated mice. CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation, regulates the intestinal flora, and protects the intestinal mucosa. It is thus a potential therapeutic agent for ulcerative colitis.

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Ciprofloxacin ; chemistry ; Cricetinae ; Cricetulus ; Drug Design ; HL-60 Cells ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; Molecular Structure ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Piperazines ; chemical synthesis ; chemistry ; pharmacology

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; Cell Line, Tumor ; Ciprofloxacin ; pharmacology ; Cricetinae ; Cricetulus ; Fluoroquinolones ; chemical synthesis ; chemistry ; pharmacology ; HL-60 Cells ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; pathology ; Mice ; Structure-Activity Relationship ; Thiadiazines ; chemical synthesis ; chemistry ; pharmacology ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

BACKGROUNDIt has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning.

METHODSSixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated.

RESULTSADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats.

CONCLUSIONSCardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.

ADAM Proteins ; metabolism ; ADAMTS1 Protein ; Aging ; metabolism ; physiology ; Animals ; Immunohistochemistry ; Ischemic Preconditioning, Myocardial ; Male ; Myocardial Infarction ; metabolism ; pathology ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

Objective To observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis. Methods Rat heart IPC model was made by 4 circles of occluding the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF-B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6, 12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD ligation 24 h after IPC, 14 days later, the anti-SM-α-actin antibody was used to detect the mature neovascularization in the border of the infracted area. Results VEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic area in IPC group compared with the control group ( P < 0. 05 ).Density of mature arteries was also significantly increased in IPC plus MI group than that in MI group (P <0. 05). Conclusion IPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.

Objective To investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model. Method Infarct size was measured by Masson's Trichrome staining, the expression of protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by immunohistochemistry and quantitative real time RT-PCR, plasma levels of adiponectin at above mentioned four time points after IPC were detected by ELISA in IPC and MI rats. Result Infarct size was smaller in IPC than in MI rats (20% ±2% vs. 31% ±3%, P＜0. 05). The expression of adiponectin mRNA at 6 h and 12 h after IPC was 2. 2 and 2. 1 times higher than in Sham rats at respective time points (P ＜ 0. 05 ). Immunohistochemistry staining evidenced increased adiponectin expression in the ischemic area and weak expression of adiponectin in non-ischemic area ( P ＜ 0. 05 ).Compared to the sham group, the plasma level of adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h:7.40 ±0.47 vs. 10.90 ±1.74;6 h: 8. 18 ±1.41 vs. 10.98 ±1.74;12 h:6. 97±1.02 vs. 9. 31 ±0. 96, P ＜ 0. 05 ). Conclusion IPC reduced infarction size, upregulated the myocardial expression of adiponectin at mRNA and protein levels, and increased plasma adiponectin concentration, suggesting that the adiponecitn may play a critical role in the protective effect of IPC.