Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by ¹H NMR, ¹³C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC₅₀ = 0.26 μmol·L^-1) was 6.7 times than the lead compound A (IC₅₀ = 1.73 μmol·L^-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

Objective To examine the changes of histological parameters of radial artery in uremia,and to explore their effects on arterial stiffness.Methods Sixty uremic patients underwent arteriovenous fistula surgery for hemodialysis and 20 healthy subjects received healthy examination were collected as uremia group and control group, respectively.Segments of radial arteries were obtained from all of uremic subjects and were evaluated by HE, Masson, van Kossa staining and electron microscopy.The expressions of osteopontin (OPN), α-SMA and elastin in arterial wall were detected by immunostaining, and apoptotic cells were determined by TUNEL assay.All of the subjects in the two groups received brachial ankle pulse wave velocity (baPWV) examination and the results were compared.The associations among histological parameters and baPWV were analyzed.Results More than one half (34/60) of artery samples presented uniformly thickening intima, in which most of cells expressed α-SMA and a few cells underwent apoptosis.The subendothelial matrix was abundant in collagen fibers, and no calcium deposition was found.The media thickened obviously, with increased collagen fibers, reduced elastin, unchanged α-SMA expression, and a few apoptotic smooth muscle cells.Two thirds uremic arteries expressed OPN, of which only one half had significant calcium deposition.The adventitia thickened and no calcium deposition was found.The baPWV level in uremic subjects was ( 18.5 ± 3.2 ) m/s, far greater than that in control subjects ( P ＜ 0.001 ).Statistical analysis showed that baPWV value was correlated with media thickness, calcification degree, and collagen content positively, and with elastin expression negatively.For diabetic uremic subjects, the OR values of vascular calcium deposition and remarkably-elevated baPWV value were 3.1, 2.3, respectively.Conclusions Radial arterial intima often presents hyperplasia which is not related with baPWV increment in uremia.Arterial media calcification and collagen content incremental are the most two protuberant characteristics in uremia, especially in ones accompanied with diabetes.Medical calcification, collagen accumulation, and e]astin reduction may contribute to the increased arterial stiffness in uremia.

Objective To investigate the expression of inflammatory mediators in renal tubular epithelial cells in patients with diabetic nephropathy (DN) and to explore the possible clinicopathological significance. Methods Twenty-three patients with DN diagnosed by renal biopsy and 10 patients with renal cell carcinoma undergone nephrectomy were allocated into DN group and control group, respectively. The renal expression of NF-κB p50, NF-κB p65, NF-κB p65 mRNA, MCP-1, OPN, α-SMA, and FN was detected by immunohistochemical or in situ hybridization assay. Serum creatinine, urinary N-acetylglucosaminedase (NAG), urinary albumin and 24-hour urinary protein were detected. The correlation between these inflmmnatory markers and clinicopathological data were analyzed. Results (1)Among all the 23 DN patients, granular degeneration of the renal tubular epithelium, focal tubular atrophy, infiltration of inflammatory cells and interstitial fibrosis were apparent, and none of these were found in control group. (2) Immunohistochemical and in situ hybridization assay showed that, compared with control group, expression of these factors increased significantly in renal tubular cells or interstitium in DN patients, and expression of α-SMA or FN was not found in tubular epithelial cells. (3)Statistics assay showed the tubular NF-κB p65 protein expression was correlated with all of the following factors: NF-κB p50 protein (r=0.792) and NF-κB p65 mRNA (r=0.763), tubular MCP-1 (r=0.825) and OPN (r=0.869) expression, interstitial α-SMA (r=0.327) and FN (r=0.432) expression, proteinuria(r=0.710), estimated glomerular filtration rate (eGFR) (r=-0.728), and urinary NAG (r= 0.930), P<0.01 respectively. Conclusion Tubular inflammation may play a role in the pathogenesis and progression of DN.

Objective To investigate whether epithelial-mesenchymal transition (EMT)is involved in the anti-invasion and anti-metastasis effects of curcumin on MDA-MB-2 3 1 breast cancer cell line and further analyze the underlying mechanisms.Methods MTT method was used to detect the anti-proliferative effect of curcumin on MDA-MB-2 3 1 cell line induced by lipopolysaccharide (LPS).The morphological changes were determined by optical and transmission electron microscopy,respectively.The expressions of Vimentin,E-cadherin,NF-κB and Snail were analyzed using RT-PCR and Western blotting.Results Curcumin could inhibit the occurrence of LPS-induced EMT of MDA-MB-2 3 1 breast cancer cell line, decrease the expression of LPS-induced EMT marker Vimentin and increase the expression of E-cadherin, resulting in the inhibition of in vitro cell motility and invasiveness.These actions were mediated by inactivating NF-κB-Snail signaling pathways.Conclusion Our data provide a new perspective of the anti-invasion mechanism of curcumin,indicating that the effect is in part due to its ability to inhibit the EMT process.

Adult ; Aged ; Carcinoma, Small Cell ; pathology ; surgery ; Carcinoma, Squamous Cell ; pathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Thymus Neoplasms ; pathology ; surgery

Objective To investigate the association of radial arterial calcification damage with bone mineral density (BMD) and bone metabolism biomarkers in uremia patients.Methods Sixty-seven incident hemodialysis patients were recruited into uremic group.Serum creatinine,calcium,phosphorus,lumbar spine and femoral neck BMD were measured.Parathyroid hormone (iPTH),25OHD,1,25(OH)2D,fibroblast growth factor (FGF) 23,bone specific alkaline phosphates (BAP) and osteocalcin (BGP),type Ⅰ collagen pyridine crosslinked C-telopcptidc (ICTP) were detected.Radial artery calcification was analyzed by von Kossa staining and transmission electron microscopy.Arterial type Ⅰ collagen (Col Ⅰ) expression was examined.Twenty-three healthy cases received serum and BMD examination only as control.Results Uremic patients presented higher serum phosphate,iPTH,FGF23,lower serum calcium,25OHD,1,25 (OH)2D (all P ＜ 0.05),and lower lumbar spine and femoral neck BMD (all P ＜ 0.01) compared to controls.Significant calcium deposit was observed in radial arteries in 24 uremic cases (35.8％),including 10 cases of diabetes.Immunohistochemistric assay confirmed that Col Ⅰ expression increased around calcification site and electron microscope revealed that more calcium and phosphorus plaque attached among collagen fibers.No correlation was showed between iPTH and radial artery calcification (r =-0.08,P =0.306),but after stratified by iPTH levels,correlation of iPTH and calcification was found in low iPTH (＜ 150 ng/L) group and high iPTH group (＞ 300 ng/L) (r =-0.41,0.31,P=0.044,0.023).Diabetes,lumbar spine and femoral neck BMD,ICTP,FGF23 were correlated with arterial calcification (r =0.62,-0.25,-0.43,0.34,0.86,P =0.000,0.001,0.012,0.018,0.000).Multiple regression analysis showed femoral neck BMD,ICTP,FGF23 levels were independently associated with radial arterial calcification (β =-0.221,0.181,0.260,P =0.021,0.024,0.036).Conclusion In uremic patients,reduced BMD,abnormal bone turnover rate,especially accelerated bone reabsorption,and increased serum FGF23 level are independently associated with radial artery calcification.

OBJECTIVETo evaluate the use of titanium mesh reconstruction after sternal tumor resection.

METHODSFrom January 2007 to January 2011, 14 patients with sternal tumors were admitted into Peking Union Medical Hospital. The clinical characteristics, surgical resection, and technique of reconstruction were reviewed.

RESULTSOf the 14 patients, 3 had a metastatic sternal tumor, the primary sites of which were as follows: hepatic carcinoma in one case (metastasis 19 years after operation), breast carcinoma in another case (metastasis 5 years after operation), and renal carcinoma in the other case (found simultaneously). Two patients showed local involvement of the sternum: 1 had thymic carcinoma, and the other had myofibrosarcoma. The remaining 9 patients had primary tumors: 4 were osteochondroma, 3 chondrosarcoma, 1 eosinophilic granuloma, 1 non-Hodgekin's lymphoma. En bloc resection of the sternal tumor was performed in all the 14 patients. The defect was repaired with the titanium mesh adjusted to the shape of the defect and fixed with the stainless steel wire. Eleven patients were followed up for a period from 2 months to 4 years, during which no translocation or broken of the titanium mesh was observed.

CONCLUSIONSRadical en bloc excision remains the treatment of choice for sternal tumors. Sternum defect reconstruction using titanium mesh as a rigid replacement proves appropriate and effective.

Adult ; Aged ; Bone Neoplasms ; surgery ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Sternum ; surgery ; Surgical Mesh ; Titanium

Objective To observe the effect of ginsenoside Rb1,the most abundant ginsenoside in ginseng root,on differentiation and lipolysis of 3T3-L1 cells and to explore its anti-diabetic mechanism.Methods 3T3-L1 preadipoeytes were induced under standard differentiation process in the presence of 0.1,1,10,100?mol/L ginsenoside Rb_1 for 6 days.Oil red O staining,measurement of triglyceride contents and glucose uptake assay were performed.The expressions of mRNA and protein of PPAR?2,C/EBP?,ap2,glucose transporter (Glut) 1,and Glut4 were analysed with quantitative real time-PCR and Western blot.The binding affinity of Rb_1 to PPAR?-LBD was evaluated by Surface Plasmon Resonance (SPR).Lipolysis of adipocytes was examined by the measurement of glycerol released from adipoeytes treated with Rb_1 for 1 h.Results Ginsenoside Rb_1 facilitated differentiation of 3T3-L1 preadipoeytes in a dose-depondent manner.10?mol/L ginsenoside Rb_1 increased lipid accumulation by about 56%.Treatment of differentiating adipocytes with 10?mol/L ginsenoside Rb_1 increased the expressions of PPAR?2 and C/EBP?mRNA and protein,as well as mRNA expression of ap2,one of their target genes.After treatment of differentiating adipoeytes with Rb_1,basal and insulin-mediated glucose transport augmented significantly accompanied by up-regulations of mRNA and protein level of Glut4,but not of Glutl.SPR showed Rb_1 could bind to PPAR?which suggested Rb_1 was a ligand of PPAR?.Ginsenoside Rb_1 inhibited basal lipolysis in adipoeytos in a dose-dependent manner.However,it did not affect isoproterenol-stimulated lipolysis.Conclusion As a PPAR?ligand,ginsenoside Rb_1 promotes adipogenesis,inhibitas basal lipolysis and inereasos basal and insulin-mediated glucose transport in cultured adipoeytes.Therefore,anti-diabetic and insulin-sensitizing activity of ginsenosides is,at least in part,involved in the enhancing effect on PPAR?2 and C/EBP?expressions,hence promoting adipogenesis and glucose uptake,and inhibiting lipolysis in adipocytes.

The paper introduces study and development of makerspace both in China and abroad,analyzes the effect of introducing makerspace into the hospital library and proposes ideas and suggestions on building makerspace in the hospital library,including aspects like validation of positioning and target,rebuilding of space and knowledge platform and talent cultivation,etc.