BACKGROUND: Acute pancreatitis is a serious complication during pregnancy, however the incidence of hyperlipidemia induced by pancreatitis is lower. METHODS: We treated a pregnant woman with hypertriglyceridemia-associated acute gestational pancreatitis who simultaneously developed hypoxemic acute respiratory failure (ARF). RESULTS: The woman was successfully treated through noninvasive positive pressure ventilation (NPPV), emergent caesarean delivery, drainage of chylous ascites, and peritoneal lavage. CONCLUSION: The signs and symptoms of ARF were greatly improved in this patient after NPPV and conventional therapies. Early NPPV may be related to good prognosis of the disease.

Objective To explore phenotypic modulation of vascular smooth muscle cells(VSMC) and change of p38 mitogen-activated protein kinase(MAPK) expression after intimal injury of rabbit carotid arteries. Methods The model of vascular restenosis established by balloon injury of rabbit carotid common arteries was used.HE staining,immunohistochemistry staining and Western blot were used to detect the change of proliferation cell nuclear antigen(PCNA),smooth muscle ?-actin(SM?-actin),p38 expression and morphology of sham-injured arteries and injured arteries at different time points.Results ⑴The proliferating VSMC was observed on the side of the medium lumen at 1 day and on the surface of vascular lumen at 3 days after injury.The neointima was formed and gradually being thicken at 5～7 days,and the thickening was accelerated at 14～35 days after injury.⑵PCNA was negative in the medium and endothelium of sham-injured arteries.Positive cell rate of PCNA was gradually increased at 1～14 days in the medium and at 5～14 days in the neointima after injury,with the maximum rate at 14 days.However,it declined gradually after 28 days.Positive cell rate of PCNA in the neointima was slightly higher than that in the medium.⑶SM?-actin was positive in the medium,negative in the endothelium of sham-injured arteries.Positive cell area of SM?-actin initially decreased at 1 day in the medium after injury with the minimum rate at 3 days,but it increased gradually after 5 days.Expression of SM?-actin in the neointima was slightly less than that in the medium.⑷p38 expression was very low or negative in the medium of sham-injured arteries.Expression of p38 was sustained and increased at 1～35 days after injury with the most remarkable elevation at 3～14 days.Expression of p38 in the neointima was higher than that in the medium.There was positive relationship between the p38 expression and PCNA expression in the vascular wall at different time points after injury.Elevation of p38 was earlier than decrease of SM?-actin.Conclusion There was a close relationship between the phenotypic modulation and proliferating ability of VSMC.P38 participated in signal transduction of phenotypic modulation of VSMC after intimal injury.

Orthotopic liver transplantation has proven to be effective in the treatment of a variety of life-threatening liver diseases, however, the limitations of donated organs available and long-term immunosuppression provided an impetus for developing alternative therapies. Cell replacement strategies have been one major effective approach for overcoming the obstacles of organ transplantation in recent years. The exogenous cells should be able to proliferate and differentiate into mature hepatic cells after grafting. Use of mature hepatocytes is also hampered by limited tissue source and inability to proliferate and maintain the function for a long term in vitro. Embryonic stem cells are immortal and pluripotent and may provide a novel cell source for potential cell therapy. This review summarizes the mechanisms of controlling early liver development and hepatic differentiation of visceral endoderm in embryoid bodies, and provides an overview of diverse differentiation systems in vitro and in vivo that were applied to hepatic research in recent years. Several studies have demonstrated that ES cell-derived hepatocytes can incorporate into liver tissue and function in vivo , but a few of them have shown complete restoration of liver function after transplantation into mice with liver diseases. Further studies should be made to exploit efficient methods and clinical applications of hepatocytes derived from ES cells in the future. In addition to clinical transplantation for treatment of liver diseases, ES cells can provide a valuable tool for drug discovery applications and study on of molecular basis of hepatic differentiation.
Animals ; Cell Differentiation ; physiology ; Cells, Cultured ; Embryonic Stem Cells ; cytology ; transplantation ; Hepatocytes ; cytology ; Humans ; Liver Diseases ; therapy

AIMTo develop a sensitive and specific HPLC method for determination of trigonelline in rabbit plasma, and study the pharmacokinetics in rabbit.

METHODSAfter ig of fenugreek extract and i.v. of trigonelline in rabbit, the biological samples could be well purified after precipitation of protein with methanol and acetonitrile. Asahipak NH2P-50 column was used, the mobile phase consisted of acetonitrile-water (90:10) at a flow-rate of 1.2 mL.min-1, and detection wavelength was set at UV 265 nm. The column temperature is 30 degrees C.

RESULTSThe calibration curve was linear in the range from 0.98 mg.L-1 to 31.28 mg.L-1, with r = 0.9986, the detection limit of this method was 50 micrograms.L-1. The concentration-time curves of trigonelline in rabbits after ig and i.v. administration were shown to fit one-compartment and two-compartment open model, respectively. The main parameters after ig of fenugreek extract were as follow: T1/2(Ka) was 0.9 h, T1/2(Ke) was 2.2 h, V was 0.64 L.kg-1, AUC was 1.93 mg.min.L-1. The main parameters after i.v. of trigonelline were as follows: T1/2 alpha was 10.8 min, T1/2 beta was 44.0 min, K21 was 0.044 min-1, K10 was 0.026 min-1, K12 was 0.017 min-1, AUC was 931.0 mg.min.L-1.

CONCLUSIONTrigonelline showed a middle rate of absorption and fast rate of elimination in rabbit. Meanwhile, the method is simple, accurate, with a good reproducibility, and it provide a basic method for the investigation of trigonelline and fenugreek pharmacokinetics.

Alkaloids ; blood ; isolation & purification ; pharmacokinetics ; Animals ; Antineoplastic Agents, Phytogenic ; blood ; isolation & purification ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Female ; Male ; Plants, Medicinal ; chemistry ; Rabbits ; Seeds ; chemistry ; Trigonella ; chemistry

OBJECTIVETo isolate MSCs from adult human bone marrow cells and to induce them into adipocytes.

METHODSMSCs were isolated from adult human bone marrow aspirated by Percoll and expanded in L-DMEM. The surface antigen of MSCs, CD14, CD34, CD45, CD44, VLA-1, HLA-DR and cell cycle were analysed on a FACScan flow cytometer. MSCs were cultured in adipogenisis inducing medium including insulin, 1-methyl-3-isobutylxanthine, indomethine and dexamethasone for 7 days and stained with Oil Red O.

RESULTSMSCs grew as adherent cells and expanded more than 10 passages. They were positive for CD44 and negative for CD14, CD34, CD45, HLA-DR. The expression of VLA-1 was weak. After 7 days of adipocyte inducing, about 85%of the cells displayed accumulation of lipid vacuoles, as detected by Red Oil O.

CONCLUSIONMSCs isolated and cultured from adult human bone marrow can be induced to adipogenisis committed differentiation.

Adipocytes ; physiology ; Adult ; Antigens, CD34 ; analysis ; Bone Marrow Cells ; physiology ; Cell Differentiation ; Cell Separation ; methods ; Cells, Cultured ; HLA-DR Antigens ; analysis ; Humans ; Hyaluronan Receptors ; analysis ; Lipopolysaccharide Receptors ; analysis ; Stem Cells ; physiology

This study was aimed to establish an efficient method to detect 10 common MLL fusion genes in patients with acute leukemia. Firstly, the relevant references and databases were searched to thoroughly investigate all fusion breakpoints; the primers and probes were designed according to nearly all the involved fusion types of gene. Then the multiplex real-time PCR system was established and optimized by using the established 16 positive plasmids and negative cell lines. Finally, the detection system was clinically evaluated by means of collected 54 samples of leukemia. The results indicated that the established detection system could efficiently detect all positive plasmids with sensibility to 10 copies. Four kinds of fusion gene types such as MLL-AF4, MLL-AF9, MLL-AF10, MLL-ELL could be detected in 54 samples, the sequencing of positive samples showed consistency of sequencing results with detection results. It is concluded that a novel multiplex real-time PCR detection method is established which can detect 10 common MLL fusion genes covering about 90% of the cases harboring MLL fusions. This method is fast, sensitive, specific and reliable, and should be an useful clinical tool for identification and management of leukemia patients with MLL fusions.
Acute Disease ; Cell Line ; Gene Rearrangement ; HL-60 Cells ; Humans ; Leukemia ; genetics ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics ; Real-Time Polymerase Chain Reaction

This review presents the state of the art of pH-responsive polymeric micelles for cancer drug delivery. Solid tumors have a weakly acidic extracellular pH (pH < 7), and cancer cells have even more acidic pH in endosomes and lysosomes (pH 4-6). The pH-gradients in tumor can be explored for tumor targeting and drug release in cancer drug delivery by applying pH-responsive polymeric micelles. The pH-responsive polymeric micelles consist of a corona and a core, and are made of amphiphilic copolymers, in which there are pH-responsive polymeric blocks. Two types of pH-responsive polymers-protonizable polymers and acid-labile polymers have been mainly used to make pH-responsive micelles for drug delivery. The protonizable polymers are polybases or polyacids, and their water-soluble/insoluble or charge states undergo changes with the protonation or deprotonation stimulated by external acidity, while the acid-labile polymers change their physical properties by chemical reaction stimulated by the acidity. Polymeric micelles whose core or coronas respond to the tumor extracellular acidity can be explored for triggering the fast release of the carried drug, activating the targeting group and accelerating the endocytosis of drug-loaded polymeric micelles, and those whose core or coronas respond to the tumor lysosomal acidity can be used for facilitating their escape from the lysosomes and targeting the nucleus. Various in vivo and in vitro experiments demonstrated that pH-responsive polymeric micelles are effective for cellular targeting, internalization, fast drug release and nuclear localization, and hence enhancing the therapeutic efficacy and reducing the side effect of cancer chemical therapy.
Antineoplastic Agents ; administration & dosage ; therapeutic use ; Drug Delivery Systems ; Humans ; Hydrogen-Ion Concentration ; Micelles ; Nanoparticles ; Neoplasms ; drug therapy ; Polymers ; chemistry

Objective To observe apelin and its receptor (APJ) expressions in human osteoblasts and evaluate the effect of apelin on osteoblasts.Methods The expressions of apelin and APJ in human osteoblasts were tested by RT-PCR and Western blot.After human osteoblasts were treated with apelin,cell proliferation was measured by [~3H] thymidine incorporation and cell counting.Cell function was measured by alkaline phosphatase (ALP) activity,the secreted osteocalcin level and typeⅠcollagen production .The activation of signaling cascades was tested by Western blot.Small-interfering RNA (siRNA) to blockade APJ was applied to observe effects of apelin on cell proliferation and the activation of signaling cascades.Results Both apelin and APJ were expressed in human osteoblasts.Apelin increased the proliferation and did not show the influences on ALP activity, osteocalcin secretion and type I collagen production in human osteoblasts.Apelin induced activation of phosphatidylinositol-3 kinase (PI3K) downstream effector (Akt),but not mitogen-activated protein kinase (MAPK) such as c-jun N-terminal kinase (JNK),p38 and ERK1/2 in human osteoblasts.Suppression of APJ with siRNA or LY294002 (PI3K inhibitor) abolished the apelin-induced cell proliferation and the activation of Akt.Conclusion Human osteoblasts express apelin and APJ.Apelin stimulates the proliferation of human osteoblast via APJ/PI3K/Akt pathway,but has no effect on osteoblast differentiation.

Objective To explore the correlations between monocyte immunodepression andthe levels of C-reactive protein (CRP) and fibrinogen (Fg) in patients with severe acute stroke. MethodsThis prospective study involved 53 consecutive patients admitted in the neurological intensive care unit(NICU) within 24 h after stroke onset. Blood samples were collected serially on days 1, 2, 4, 6 and 14after stroke to determine monocytic HLA-DR expression using flow cytometry. CRP and Fg weredetected on day 2 after the admission, and Graph_Pad PRISM 4.0 software was used to analyze thecorrelations among the variables. Thirty-nine concurrent patients admitted in the general ward, whocomplained dizziness without magnetic resonance imaging evidence of acute stroke, were enrolled toserve as the control group. Results The levels of CRP and Fg in the stroke group were significantlyhigher than those in the control group (P<0.05). The CRP and Fg levels were both found to inverselycorrelate to monocytic HLA-DR expression at different observational points. The correlations of CRP andFg to HLA-DR expression were the most obvious on day 2 and 4 after admission (r=-0.419, P=0.001;r=-0.434, P=0.001), respectively. Conclusion Immunosuppression of the monocytes in patients withsevere acute stroke is probably associated with the inflammatory reaction after stroke.

BACKGROUNDThe genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis.

METHODSWe enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes.

RESULTSThere were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs. 31.9%). The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types (24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P = 0.047). Clinical stage (IV vs. IIIb), response to the first-line chemotherapy (partial vs. no) and EGFR genotype were independent prognostic factors.

CONCLUSIONPlasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Plasmids ; genetics ; Receptor, Epidermal Growth Factor ; genetics ; Survival Rate