Aged ; Humans ; Non-alcoholic Fatty Liver Disease/etiology* ; China/epidemiology*

Neurofibrillary pathology of abnormally hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) and other tauopathies. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway is pivotal for tau phosphorylation. Inhibition of soluble epoxide hydrolase (sEH) metabolism has been shown to effectively increase the accumulation of epoxyeicosatrienoic acids (EETs), which are cytochrome P450 metabolites of arachidonic acid and have been demonstrated to have neuroprotective effects. However, little is known about the role of sEH in tau phosphorylation. The present study investigated the role of a sEH inhibitor, 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl] urea (TPPU), on HO-induced tau phosphorylation and the underlying signaling pathway in human embryonic kidney 293 (HEK293)/Tau cells. We found that the cell viability was increased after TPPU treatment compared to control in oxidative stress. Western blotting and immunofluorescence results showed that the levels of phosphorylated tau at Thr231 and Ser396 sites were increased in HO-treated cells but dropped to normal levels after TPPU administration. HOinduced an obvious decreased phosphorylation of GSK-3β at Ser9, an inactive form of GSK-3β, while there were no changes of phosphorylation of GSK-3β at Tyr216. TPPU pretreatment maintained GSK-3β Ser 9 phosphorylation. Moreover, Western blotting results showed that TPPU upregulated the expression of p-Akt. The protective effects of TPPU were found to be inhibited by wortmannin (WT, a specific PI3K inhibitor). In conclusion, these results suggested that the protective effect of TPPU on HO-induced oxidative stress is associated with PI3K/Akt/GSK-3β pathway.
Cell Survival ; drug effects ; Enzyme Inhibitors ; pharmacology ; Glycogen Synthase Kinase 3 beta ; metabolism ; HEK293 Cells ; Humans ; Hydrogen Peroxide ; toxicity ; Oxidative Stress ; Phenylurea Compounds ; pharmacology ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Piperidines ; pharmacology ; Protein Processing, Post-Translational ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; tau Proteins ; metabolism

To investigate the effect of Tanreqing injection on immune activity of peripheral blood lymphocytes of patients with lung cancer. The peripheral blood lymphocytes of patients with lung cancer and healthy persons were separated by the density gradient centrifugation method for subsequent experiments, with those from healthy persons as the positive control. The effect of Tanreqing injection on stimulating the proliferation of lymphocytes with phytohemagglutinin (PHA) was determined by MTT method. The effect of Tanreqing injection on the lymphocyte secretions of IFN-γ and TNF-α and the subset ratio of lymphocytes cultured separately or with Tanreqing injection of different concentrations were examined by ELISA and flow cytometry (FCM) respectively. In addition, the LDH release assay was used to detect the cytotoxicity of cytotoxic T cells (CTL) and natural killer cells (NK). According to the findings, all of immunological indexes of lymphocytes from patients with lung cancer were weaker than that of healthy persons, but with the obvious increases in proliferation activity and IFN-γ and TNF-α secretions of lymphocytes co-cultured with Tanreqing Injection (P < 0.05). Among lymphocyte subsets co-cultured with Tanreqing Injection, CD3+, CD3+ CD4+ and CD3- CD16 + 56+ cell ratios notably increased, whereas CD4+ CD25+ Treg cell ratio obviously decreased (P < 0.05). In the meantime, Tanreqing injection can markedly promote the cytotoxicities of CTL and NK (P < 0.05). In conclusion, Tanreqing injection shows a significant effect in promoting the immune activity of lymphocytes from patients with lung cancer and their anti-tumor immunity.
Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Interferon-gamma ; genetics ; immunology ; Killer Cells, Natural ; drug effects ; immunology ; Lung Neoplasms ; drug therapy ; genetics ; immunology ; physiopathology ; T-Lymphocytes, Cytotoxic ; drug effects ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology

Objective To investigate the effects of knee replacement postoperative on reducing hemoglobin by the different doses of tranexamic acid application.Methods A total of 116 knee replacement patients were enrolled and divided into the treatment group and the control group , 58 cases in each group .The surgical procedures and methods of the two groups were same , as patients in the control group were given intrave-nously before incision tranexamic acid 50 mg? kg -1 , and those in the treatment group received tranexamic acid 100 mg? kg -1 . During the peri-operative phase , the index of operation time , incision size , blood loss during operation , post -surgery drainage and the total number of blood transfusion , as well as hemoglobin were observed . Results Patients in two groups were all discharged after successful com-pletion surgery .The blood loss , postoperative drainage , the total amount of blood transfusion of the treatment group were significantly less than those of control group ( P<0.05 ) .The postoperative values in the two groups were showed significantly decreased ( P<0.05 ) , but preoperative hemoglobin values of the treatment group were significantly higher (P<0.05).The data of preoperative and postoperative coagulation indicators compared between two groups showed no significant difference .Patients were followed up for 3 months.The incidence of complications of deep vein thrombosis (1 case), acute myocardial infarction ( 0 case), transient neuro-logical symptom (1 case) in the treatment group were significantly lower than that in control group (5, 3, 4 cases) (P<0.05).Conclusion High dose of tranexamic acid applications can reduce blood loss and transfusion knee re -placement volume , and relieve the postoperative decrease of hemoglobin , meanwhile , it has no obvious effect on coagu-lation function with defined security .

OBJECTIVETo assess the clinical features and therapeutic effect of free thin anterolateral thigh flap for the reconstruction of intraoral defects.

METHODSThe clinicopathologic data of 34 cases with oral carcinoma were obtained from Institute and Hospital of Stomatology, Nanjing University Medical School, from December 2008 to December 2011. These 34 patients underwent the simultaneous tumor resection and intraoral defects reconstruction with free thin anterolateral thigh flaps. The defects were located at tongue, buccal, mouth floor, and so on. The subcutaneous fat thickness of the flap at the site of the perforator is usually measured by ultrasound before the operation. If the thickness of the subcutaneous fat at the site of the perforator exceeded 1.5 cm, the patient was excluded from the study.

RESULTSThere were 16 male and 18 female patients. The mean age was 55.4 years. Among the 34 patients, 26 flaps with musculocutaneous perforators and 8 flaps with septo-cutaneous perforators were used. Partial flap necrosis occurred in 2 patients.

CONCLUSIONSThe free thin anterolateral thigh flap is the ideal soft tissue flap for the intraoral defects reconstruction. Satisfactory functional results can he achieved at recipient area with minimal morbidity at the donor site area.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Mouth Neoplasms ; surgery ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; methods ; Soft Tissue Injuries ; etiology ; surgery ; Surgical Flaps ; Thigh

The purpose of this study was to develop docetaxel-poly (lactide-co-glycolide) (PLGA) loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows: the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate (TPGS) was 0.2%, the ratio of oil phase to water phase was 1:5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was (40.83±2.1)%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere® and play great roles in future.
Acetone ; chemistry ; Antineoplastic Agents ; chemistry ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Drug Compounding ; methods ; Ethanol ; chemistry ; Fractional Precipitation ; methods ; Lactic Acid ; chemistry ; Microscopy, Electron, Scanning ; Nanoparticles ; chemistry ; ultrastructure ; Nanotechnology ; methods ; Particle Size ; Polyethylene Glycols ; chemistry ; Polyglycolic Acid ; chemistry ; Succinates ; chemistry ; Surface Properties ; Taxoids ; chemistry ; pharmacokinetics

OBJECTIVETo assess the clinical features and therapeutic efficacy of anterolateral thigh (ALT) flaps for the intraoral defects reconstruction.

METHODSThe clinicopathologic data of 67 cases with oral tumors were obtained from School of Stomatology, Nanjing University Medical Center from Dec. 2008 to Dec. 2010. All the patients underwent the simultaneous tumor resection and intraoral defects reconstruction with free anterolateral thigh flaps. The defects included the tongue, buccal, gingival, mouth floor, and so on. The descending branch of lateral femoral circumflex artery was anastomosed to the external maxillary artery or superior thyroid artery; the vein was anastomosed to the common facial vein or external jugular vein. The flaps were divided into three types: musculocutaneous ALT flap, fasciocutaneous ALT flap and thinned ALT flap.

RESULTSThere were 38 male patients and 29 female. The anterolateral thigh flaps included 35 musculocutaneous flaps, 17 fasciocutaneous flaps and 15 thinned flaps. The success rate was 98.5% (66/67). Partial necrosis happened in one case with diabetes, which healed after debridement and dressing. 1 flap was totally necrosis. Double venous anastomosis was performed in 41 flaps, and one venous anastomosis was performed in 26 flaps. 8 patients required operative exploration in the perioperative period including 6 flaps with thrombotic events (5 flaps were complete survival after the salvages, and 1 flap was failure) , 1 flap with hematoma, and 1 flap with twisting of perforator. The follow-up period ranged from 2 to 24 months( mean, 8.7 months). The result was satisfied. The donor sites were closed directly in all patients, and the wounds healed uneventfully.

CONCLUSIONSThe free anterolateral thigh flap is an ideal soft tissue flap for the intraoral defects reconstruction with good functional result at recipient area and less morbidity at the donor site.

Adult ; Aged ; Female ; Free Tissue Flaps ; Humans ; Male ; Middle Aged ; Mouth Neoplasms ; surgery ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; methods ; Thigh ; surgery

BACKGROUNDAttention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.

METHODSThis 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent-rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.

RESULTSA total of 1447 children with ADHD (mean age (9.52 ± 2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P < 0.001) improvement with OROS-MPH (mean: 6.95 ± 2.71) versus the score at baseline (10.45 ± 2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study.

CONCLUSIONThis open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Child ; Delayed-Action Preparations ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Prospective Studies ; Treatment Outcome

OBJECTIVETo investigate the application of titanium mesh and free forearm flap for reconstruction of maxillary defect resulted from tumor resection.

METHODSFrom 2004 to 2008, 19 cases with maxillary tumor underwent tumor resection. The defects were reconstructed immediately with titanium mesh for bony defects and free forearm flap for oral mucosa defects.

RESULTS16 cases achieved satisfactory functional and cosmetic results. The speech assessment was good without oronasal reflux. The titanium mesh was exposed and infected in 3 cases. Then the meshes were taken out and the defects were covered with the forearm flap to close the oronasal fistula. The midface was slightly depressed with no functional morbidity.

CONCLUSIONSIt is simple and practical to reconstruct maxillary defect with titanium mesh and free forearm flap. Both the functional and cosmetic results are satisfactory.

Adolescent ; Adult ; Aged ; Female ; Forearm ; surgery ; Humans ; Male ; Maxillary Neoplasms ; surgery ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; Surgical Flaps ; Surgical Mesh ; Titanium ; Young Adult

OBJECTIVETo investigate the anti-tumor effect of a novel gene-viral therapeutic system CNHK300-murine endostatin (CNHK300-mE) on gastric cancer.

METHODSSGC-7901 gastric cancer cells (5 x 10(7) cells/mouse) were injected s.c. into the right flank of Balb/c nude mice, grown to 4-5 mm to demonstrate tumor take, and 10(9) pfu/100 microl CNHK300-mE virus was injected into tumors. Tumor sizes were measured with calipers every other day. Serum samples were obtained by retro-orbital puncture and level of endostatin expression in serum was quantitated by ELISA. Fifteen days after treatment, all mice were sacrificed and tumors were excised for immunohistochemical staining of PCNA, hexon and vWF. Tumor cell apoptosis was detected by TUNEL method.

RESULTSFrom the 7th day post-treatment, the bearing tumors of mice treated with CNHK300-mE were significantly smaller than those of control group treated with PBS. Seven days after treatment, expression of endostatin was (2115 +/- 770) ng/ml, significantly higher than that of control group. Immunohistochemical staining indicated that hexon was expressed in treated tumor cells, and PCNA LI (label index) [(55.0+/-1.4)% vs control (74.1 +/- 0.4)%, P<0.05], microvessel density (MVD) of CNHK300-mE treated tumors decreased significantly. Apoptosis obviously increased in tumor cells[(78.4 +/- 9.1)% vs control (15.2 +/- 0.5)%, P<0.01]. Apoptosis bodies and crystal grid were found in tumor cell nuclear by electron microscope.

CONCLUSIONSGene-viral therapeutic system CNHK300-murine endostatin can replicate in gastric cancer cells. The mouse endostatin gene cloned into CNHK300-mE expressed in high level. CNHK300-mE may induce tumor cells apoptosis, reduce the expression of PCNA and efficiently suppress gastric cancer growth through inhibiting tumor angiogenesis.

Adenoviridae ; genetics ; Animals ; Endostatins ; genetics ; Female ; Genetic Therapy ; Genetic Vectors ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Stomach Neoplasms ; therapy ; Telomerase ; genetics ; Transfection ; Xenograft Model Antitumor Assays