Sphingolipids are structural components of cellular membranes.Their metabolites,such as ceramide,sphingosine,and sphingosine 1-phosphate are important bioactive molecules,which act as the first or second messengers regulating various cellular activities,including proliferation,survival,migration and neovascularization in vitro and in vivo tumor models.Sphingosine kinases 1(SPK1) is a critical regulator of the balance between ceramide and S1P.Recent studies show that ceramide,SPK1 and S1P can regulate many of the hallmarks of cancer.These studies suggest that these metabolites can serve as novel targets for cancer therapy.

Combining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship (SAR) has been explored.
Adenosine Diphosphate ; Drug Design ; Phthalic Acids ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Sulfonamides ; chemical synthesis ; chemistry

Objective To evaluate the potential relationship between isoforms of BRCA1 associated RING domain 1 ( BARD1 ) and the pathophysiologic markers of sporadic breast carcinoma of female Han ethnic group. Methods The expression of BARD1 isoforms in 39 breast carcinomatous tissue, 12paracancerous-normal breast tissue and 7 controlled normal breast tissue was detected by reverse transcription polymerase chain reaction (RT-PCR) and then cloned and sequenced.The difference of isoforms expression and their clinical significance were analyzed. Results There were four transcriptive products of BARD1 found in all these candidates,named full lenth,isoform γ,isoform δ and isoform e.The positive rate of isoform γ and δ was higher in carcinomatous tissues than in paracancerous-normal tissues and normal breast tissue in healthy women ( P ＜ 0.05 ). Carcinomatous tissue expressed more kinds of isoforms.There was significant difference between carcinomatous tissue and paranormal/nomal tissue ( P =0.0075 ).There was significant correlation between isoform ε positive and poor prognosis factors such as poorly differentiation,HER2 positive,poor pathologic type and larger breast cancer lumps(P ＜ 0.05 ). Conclusions There are significant differences in the expression of BARD1 isoforms among different kinds breast tissues in the female Han ethnic group.Positive isoform ε may predict poor prognosis of breast carcinoma in the female Han ethnic group.

Objective To study the characteristics of articles,citations and authors in Chinese Critical Care Medicine (Chin Crit Care Med).Methods The date about articles,citations and authors of Chin Crit Care Med from 2005 to 2006 were collected and analyzed in terms of bibliomertic parameters.Results There were 612 papers published in Chin Crit Care Med during 2 years and the papers with funded projects were accounted for 63.1%.The authors came from 30 provinces,autonomous regions and municipalities directly under the central government in China.The average number of articles per issue was 26;the paper density was 0.40 and the average period from the date of submission to publication was 5.2 months.Among these papers,87.6% were shared with co-authors,with cooperation rate of 4.40.The papers with citation were accounted for 85.1% and 95.9% of the citations in English came from journals.The Price's index was 58.2%.Conclusion The articles published in Chin Crit Care Med have high quality.It is one of the most important resources of information for researches in this field,and it is also a primary kernel journal in Chinese medicine field.

Objective To investigate the effect of microcireulation blood flow and altering immunity by Chuanxiongqin,ulinastain and thymosin α1 on sepsis patients.Methods 90 patients were randomly divided into 3 groups(n=30),namely ICU group,Chuanxiongqin group,ulinastain and thymosin α1 group.HLA-DR/CD14+and IL-6,TNF-α,Lac,DD were measured.Results (1)DD showed no significant difference at every time point between ICU group and ulinastain+thymosin α1 group(P＞0.05).DD decreased in Chuanxiongqin group,and was significantly different from the others on the third day.(2)Lac unchanged significantly at every time point in ICU group(P＞0.05).Lac in Chuanxiongqin group and ulinastain+thymeain α1 group tended to decrease,and was statistically different from ICU group on the second day.(3)IL-6 and TNF-α tended to increase at every time point in ICU group(P＜0.05).In ulinastain+thymosin α1 group,IL-6 and TNF-α returned to the level before treatment,HLA-DR/(D14+increased significantly,and was higher than Chuanxiongqin group and ICU group statistically.Conclusion Chuanxiongqin could ameliorate circulation;ulinastsin and thymosin α1 could depress IL-6,TNF-α.So ulinastain and thymosin α1 might protect the immunity of sepsis patients.

Background The surgery for femtosecond laser created laser in situ keratomileusis(LASIK)flaps has made great progression recent year,but the postoperative corneal wound healing and regeneration of nerve fibers after surgery are closely concerned.Objective This study was to compare and analyze the clinical outcomes between FEMTO LDV femtosecond laser flap and mechanical microkeratome Hansatome flap in LASIK.Methods A prospective case-controlled study was designed.The serial 38 myopic eyes of 38 patients were included from March through July,2010 in Henan Armed Police Force General Hospital.The patients were randomized into FEMTO LDV femtosecond laser assisted flap group(20 patients/20 eyes)and mechanical microkeratome Hansatome assisted flap group(18 patients/18 eyes)with the matched age,gender and refraction of spherical equivalent.HRT Ⅲ examinations were performed before surgery,1 week,1 month and 3 months after surgery to compare the morphological changes atthe center and margin of the flaps,and evaluate the similarities and differences of cellular morphology after surgery between the two approaches.Written informed consent was obtained from each patient prior to this medical trial.Results The best corrected visual acuity was ≥ 1.0 and the refract diopter was similar in both groups(+0.21 D±0.48 D and-0.04 D±0.54 D)1 month after LASIK.The corneal thickness was insignificant increased in the first week after LASIK,and the density of shallow stromal cells was decreased in 1 week,1 month and 3 months compared with pre-operation in the femtosecond laser assisted flap group(t =-27.99,-25.49,-28.87,P ＜ 0.01).In the Hansatome assisted flap group,significantly thickened corneal epithelium was seen in the first week after LASIK compared before LASIK(56.73 μm±2.47 μm versus 51.16 μm±1.11 μm)(t=9.29,P＜0.05),and the density of shallow stromal cells was decreased in 1 week,1 month and 3 months compared with pre-operation in the Hansatome assisted flap group(t =-17.57,-14.13,-19.63,P =0.00).The density of high reflective interface particles in cornea was lower in 1 week,1 month and 3 months after LASIK in the femtosecond laser assisted flap group than that in the Hansatome assisted flap group,showing significant differences between them(t =-13.505,-11.900,-14.084,P＜0.01).The active stromal cells were seen beneath the interface in both groups in the first week and gradually decreased after that time.Intact corneal nerve fibers were found in the femtosecond laser assisted flap group,but those in the Hansatome assisted flap group were shorter and smaller 3 months after LASIK.At 3 months after surgery,the flap margin showed stromal higher reflection and irregular secondary fibrosis in the femtosecond laser assisted flap group,and in contrast,the flap margin had the appearance of a unclearly identified fibrotic scar in the Hansatome assisted flap group.Conclusions Compared with the LASIK and Hansatome assisted flap,the LASIK with FEMTO LDV flap shows earlier nerve fiber regeneration and greater fibrotic scarring,which imply a good wound healing process in the LASIK with FEMTO LDV flap.

OBJECTIVE: To investigate the culture of endothelial progenitor cells (EPCs) from peripheral blood in patients with coronary heart diseases (CHD) before and after percutaneous coronary intervention (PCI), and to observe the cells shape and determine the cell number and proliferation activity. METHODS: Ninety-five patients were divided into a CHD group(n=65) and a control group (n=30). The mononuclear cells were isolated from peripheral blood of patients with CHD before, right after and 4 days after PCI by Ficoll-density centrifugation. The isolated cells were cultured in RPMI1640 medium supplemented with VEGF165 and bFGF.EPCs were characterized as adherent cells of double positive for DiL-acLDL uptake and FITC-UEA-I binding by direct fluorescent staining under a fluorescence microscope. The EPCs specific surface mark CD34 and KDR were assessed by fluorescence activated cell sorter analysis. The cell shapes were analysed and the number of colony-forming units(CFU) was counted by phase-contrast microscope. RESULTS: The number of EPCs reduced in patients with CHD before the PCI, but the cell number was significantly increased in patients with CHD after the PCI, and the number reduced in patients with CHD 4 days after the PCI. How-ever, the number of CFUs did not change in patients before and after the PCI. CONCLUSION PCI can increase endothelial progenitor cells in patients after the PCI; but 4 days after the PCI, this increase will not exist.
Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; Cell Adhesion ; Cell Count ; Cell Movement ; Cells, Cultured ; Coronary Disease ; blood ; therapy ; Endothelial Cells ; pathology ; Female ; Humans ; Male ; Middle Aged ; Stem Cells ; pathology

OBJECTIVE: To explore the effect of melatonin(Mel) on the proliferation, apoptosis and expression of bcl-2 in oxidized low-density lipoprotein(ox-LDL)-induced endothelial progenitor cells (EPC) from human umbilical cord blood in vitro. METHODS: Total mononuclear cells were isolated from human umbilical cord blood in vitro by Ficoll density gradient centrifugation, and the cells were plated on fibronectin-coated culture dishes. After 7 days, the attached cells were divided into 7 groups: a control group (normal cells), 3 ox-LDL groups[the attached cells were incubated with different concentrations of ox-LDL(5,10,and 20mg/L) for 24 hours], and 3 Mel groups[the attached cells were incubated with different concentrations of Mel (0.5,1.0, and 2.0 mmol/L) respectively for 24 hours before incubation with 10 mg/L ox-LDL]. EPC was identified by examining the expression of CD34, vascular endothelial growth factor receptor-2(VEGFR-2) and CD133 under a laser scanning confocal microscope. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to detect the effect of Mel and ox-LDL on the multiplication ability of EPC. Flow cytometry was used to detect the apoptosis. The expressions of Bcl-2 mRNA and protein were detected respectively by RT-PCR and immunohistochemistry technology. RESULTS: After being exposed to the ox-LDL, the proliferation of EPC in the 3 ox-LDL groups was lower, and the apoptosis rate was higher than that in the control group in a dose-dependent manner (P<0.01); Mel was added at different concentrations before the ox-LDL incubation, and the cells in the 3 Mel groups showed higher proliferation and lower apoptosis rate than those of the 3 ox-LDL groups (P<0.01). Expression of Bcl-2 mRNA and protein of EPC in the 3 Mel groups was higher than that in the 3 ox-LDL groups (P<0.01). CONCLUSION Ox-LDL can inhibit the proliferation of EPC and promote the apoptosis of the cells by down-regulating the bcl-2 expression. Mel can inhibit these effects of ox-LDL.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; Humans ; Lipoproteins, LDL ; adverse effects ; Melatonin ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stem Cells ; cytology ; drug effects

Objective To evaluate the acute and delayed killing effect of high intensity focused ultrasound (HIFU) on Echinococcus granulosus(E. granulosus)protoscolices in vitro.Methods E. granulosus protoscolices were treated with different dosage of effective power(0,25,50,100,200,250 W)and time(5,10,20,30,40,50,60 s)of HIFU in vitro to obtain the dosage-effect curves.Then the survival pmtoscolices were incubated,and the mortality of each group was counted daily.The protoscolicidal effects were investigated by trypan blue exclusion assay.Results Compared with the untreated group,the Vitality of E.granulosus protoscolices significantly decreased immediately after treated by HIFU of different dosage(F=5201.59 vs 1865.65,P＜0.05),there were the interaction both different dosage and time(F=214.50,P＜0.05).The protoscolices were broken into pieces by HIFU of 250 W×40 s,whereas the growth of the surviving protoscolices after exposed to HIFU was obvious suppressed.Both the acute killing effect and the delayed inhibitory effect showed a dosage-dependant manner.The inhibitory effect increased along with the increased dosage of HIFU(P＜0.05).The inhibitory effect in 50 W×10 s group was stronger than 25 W×20 s group(P＜0.05).The mortality was increased in parallel with the increase of HIFU dosage.Conclusions HIFU show an effective immediately killing effect,as well as a growth-inhibiting effect on the E.granulosus protoscolices in vitro.

Objective To investigate the clinical and mammographic features of plasma cell mastitis.Methods Twenty-five patients(28 lesions)with histologically confirmed plasma cell mastitis, aged from 26 to 70 years(mean age 41 years),were examined with X-ray mammography.The clinical manifestations and imaging features were retrospectively reviewed.Results No case was in lactation.The painful irregular masses,ranged from 1.3 to 8cm in size,were found in 22 patients,while 3 patients with acute episode.Recurrent episodes of breast masses were noted in 4 patients.Based on the mammographic appearances,the plasma cell mastitis were classified as the following four types:inflammation-like type (2/28),ductal ectasia type(3/28),focal infiltration type(10/28)and nodular type(13/28).The valuable radiogyaphic signs:(1)An asymmetrically increased density along the lactiferous duct with a flame-like appearance,inhomogeneous low density tubular structures and scattered stick-shape calcifications.(2) Architectural distortion and oil cysts formation in adjacent area,(3)Subareolar ductal ectasia.Conclusions The clinical and mammographic characteristics of plasma cell mastitis are critical to avoiding unnecessary surgery.Histopathological result is needed for the diagnosis in patients highly suspected of malignancy.