Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Immunophenotyping ; Leukemia ; diagnosis ; immunology ; therapy ; Male ; Middle Aged ; Neoplastic Stem Cells ; immunology ; Prognosis ; Treatment Outcome ; Young Adult

Objective To evaluate the system of academic assessment and evaluation on introduced talented personnel so as to establish a consummate talented personnel introduction mechanism and to further standardize the introduction work. Methods On the basis of referring to document papers and soliciting management as well as human resource experts iteratively,the research method of expert consultation was adopted.(Results)The index system of academic assessment and evaluation on introduced talented personnel in school of medicine was preliminary established,and the objective index and subjective evaluation were scientifically combined to form the method of academic assessment and evaluation on introduced talented personnel. Conclusion Through simulative assessment and evaluation as well as probational demonstration,there exits definite scientificality and applicability on this academic assessment and evaluation index system,and it can provide a properly objective evaluation and essential reference foundation in the aspect of introducing more advanced talented personnel in the near future.

Adrenocorticotropic Hormone ; blood ; Animals ; Female ; Hypoxia ; metabolism ; Male ; Rats ; Rats, Wistar

Sphingosine 1-phosphate (S1P) is an important biologically active lysophospholipid that transmits signals through a family of G-protein-coupled receptors (GPCRs) to regulate the vital functions of several types of immune cells. The S1P GPCRs suppress both generation of specialized functional cytokines, such as IFN-gamma and IL-4, and proliferation of T-cells. Although S1P is chemotactic to T cells, B cells, dendritic cells, and natural killer cells, the major effect of S1P on the immune system is the regulation of lymphocyte recirculation and tissue distribution by S1P and S1P1. Chemotactic response of CD4+CD25+ regulatory T cells to S1P is reduced, but its optimal suppressive activities require S1P. FTY720, a new class of immunomodulator, is rapidly phosphorylated by sphingosine kinase 2 in vivo to form the biologically active phosphorylated-FTY720 (FTY720-P), which closely resembles S1P. The FTY720-P is a true agonist for S1P1, S1P3, S1P4, and S1P5, it affects the tissue distribution and functional activity of T cells, B cells, dendritic cells and regulatory T cells. FTY720 were demonstrated to be a hypotoxic, great effective and reversible immunosuppressive efficacy to prevent allograft rejection and treat some autoimmune diseases. In this article, the synthesis and metabolism of S1P, the expression of S1P GPCRs in immune cells, the effect of S1P on immune cells, the drugs targeted to S1P GPCRs and their clinical implications are reviewed.
Fingolimod Hydrochloride ; Humans ; Immunomodulation ; physiology ; Lysophospholipids ; immunology ; physiology ; Propylene Glycols ; metabolism ; Receptors, G-Protein-Coupled ; immunology ; physiology ; Sphingosine ; analogs & derivatives ; immunology ; metabolism ; physiology

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

The type of basic media and the contents of plant growth substances were investigated by orthogonal design experiment,and also the effects of different culture conditions on the growth of suspension cells and the accumulation of total flavonoids in Eucommia ulmoides were studied.The results showed that B5 medium supplemented with 0.5mg/L NAA,0.6mg/L 6-BA and 30g/L sucrose,at initial pH 5.0～5.5,20g(FW)/L inoculation quantity and 110 r/min of rotation speed was a preferable culture conditions for E.ulmoides suspension cells growth and flavonoids synthesis.The results of metabolic kinetics analysis for E.ulmoides cell suspension culture showed that the logistic and Luedeking-Piret equations can be used for describing the kinetics of cell growth,sucrose consumption and flavonoids production during the process.The maximum specific growth rate(?m),the actual growth yield based on sucrose(YG) and maintenance coefficient(m) were 0.417/d,0.619g/g and 0.0206g/(g?d-1) respectively.All these outcomes could give a basis for establishing the suspension cell culture of E.ulmoides and production of the natural active components in large-scale.

70 bpm during scan),the proportion of segments that could not be assessed because of motion artifact were 0.1%(1/759),1.1%(7/649),2.5% (10/407),42.6%(103/242),and 75.5%(108/143),respectively.With conventional selective coronary angiography as the golden standard,the sensitivity,specificity,positive and negative prediction values to detect≥50% stenotic lesions in the assessable segments were 79.2%,96.0%,83.8%,and 94.6%,respectively.There was a significant correlation between the number of segments per patient not assessable because of motion artifact and heart rate during the scan(r=0.655,P=0.000).Conclusion MSCT is capable of achieving high accuracy for detection of coronary artery stenosis,and is a reliable technique to diagnose coronary artery disease.

Objective To evaluate the safety of surgical procedures for patients after heart valve prosthesis implantation.Methods Clinical data of 12 cases with heart valve prosthesis implantation undergone other surgical treatment from November 1996 to December 2005 were retrospectively analyzed.All the cases had routine oral warfarin with prothrombin time (PT) of 20.0—28.3 s averaged 23.5 s, international normalized ratio (INR) for prothrombin of 1.79—2.23 averaged 1.95 and heart functional class Ⅰ—Ⅲ.Among them,appendectomy was performed in three cases with acute appendicitis,reposition and repair in one with inguinal hernia,radical gastrectomy in two with gastric carcinoma,left hemicolectomy in one,cholecystectomy in three,left femoral head replacement in one,and bilateral high ligation and ablation of great saphenous vein in one.Elective surgical operation was performed in seven cases,and emergency operation in five.In those with elective surgery,warfarin was stopped 2—3 days before operation,while 5—10 mg vitamin K_1 was injected intramuscularly 6—8 hours before emergency surgery with preoperative median PT of 15.1 and 15.3 s and median INR of 1.24 and 1.30,respectively.In operation,5—10 mg vitamin K_1 were injected intravenously into the patients by drip depending on their bleeding on the surface of wound.ECG,blood pressure,hemoglobin and oxygen saturation were routinely monitored for all the cases intraoperatively and postoperatively.For the cases with heart function above class Ⅱ,fluid infusion was adjusted based on intubated central venous pressure,and for those with general anesthesia,analyses of blood gases and electrolyte were monitored routinely in operation.Results OPeration time averaged 20—160 rain in all the 12 patients,with blood loss 5—280 ml in average and without complications of massive hemorrhage,thrombosis and heart failure.Conclusions Surgical operation was safe for patients with heart valve prosthesis implantation,if preoperative PT and INR were adjusted to about 15 s and 1.30,respectively by cessation of warfarin or application of vitamin K_1,combined with careful manipulation and strengthened perioperative management.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

Aim The effect of tetrandrine on TGF-?1 mRNA expression in glomerulosclerosis rat was observed. Methods The rats were randomly divided into four groups, such as the normal control group (sham operative rat), glomerulosclerosis model group,tetrandrine group and amlodipine group. The expression of TGF-?1 mRNA was analyzed by Northern blot hybridization. Results The expressions of TGF-?1 mRNA in two treating groups were much lower than untreated model group. There were no difference between these two treating groups. Conclusion Tetrandrine can decrease the expression of TGF-?1 mRNA in glomerulosclerosis rat induced by unilateral renctomy plus adriamycin.